Responsive image
博碩士論文 etd-1223110-233205 詳細資訊
Title page for etd-1223110-233205
論文名稱
Title
抗憂鬱藥物Paroxetine與Nortriptyline對攝護腺癌PC3細胞株細胞內鈣離子相關訊息傳遞及細胞凋亡之影響
The effects of antidepressants paroxetine and nortriptyline on intracellular Ca2+-related signal transduction and cellular apoptosis of PC3 human prostate cancer cells
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
140
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2010-12-08
繳交日期
Date of Submission
2010-12-23
關鍵字
Keywords
鈣離子訊息、細胞凋亡、攝護腺癌細胞
apoptosis, Ca2+ signal, PC3, paroxetine, nortriptyline
統計
Statistics
本論文已被瀏覽 5685 次,被下載 0
The thesis/dissertation has been browsed 5685 times, has been downloaded 0 times.
中文摘要
憂鬱症是21世紀影響人類健康的重要疾病,抗憂鬱藥物可改善憂鬱症狀,ㄧ般相信神經傳導物質在藥理作用機轉上扮演了重要角色,但對於抗憂鬱藥物如何影響細胞內訊息傳遞系統,目前所知仍十分有限。本論文主要是探討新ㄧ代抗憂鬱藥物paroxetine與傳統三環抗憂鬱藥物nortriptyline對攝護腺癌細胞鈣離子訊息及細胞凋亡之影響。
藉由fura-2螢光的方式,我們發現paroxetine(10-150 μM)與nortriptyline(50-500 μM)可以增加攝護腺癌細胞內鈣離子濃度,且反應程度與藥物濃度成正相關。將細胞外鈣移除,部分減少鈣離子上升的幅度,代表細胞外的鈣離子的流入與細胞內胞器中鈣離子的釋放,都與鈣離子濃度增高有關。在不含細胞外鈣的環境中,先將「內質網鈣離子幫浦抑制劑」加入攝護腺癌細胞,被動排空內質網內鈣離子,幾乎會完全抑制paroxetine與nortriptyline造成的鈣離子濃度上升。相反地,先以nortriptyline處理,也明顯減少「內質網鈣離子幫浦抑制劑」所造成的鈣離子濃度升高,如此可證明抗憂鬱藥會造成內質網鈣離子流出。若先以U73122抑制磷酯酶C的活性,將減少80% paroxetine所造成的鈣離子濃度上升,但並不影響nortriptyline的作用。Paroxetine造成的鈣離子濃度變化會被鈣池調控鈣離子通道阻斷劑econazole與SK&F96365,磷酯酶A2抑制劑aristolochic acid,與蛋白質激酶C調控劑所抑制。蛋白質激酶C的活化可抑制nortriptyline造成之鈣離子濃度上升。10 μM norrtriptyline可增加細胞的生存能力,但50 μM Nortriptyline會殺死40%細胞且導致明顯的細胞凋亡。
綜合上述結果我們可以知道,paroxetine可藉由與磷酯酶C相關的內質網鈣離子釋放與鈣池調控的細胞外鈣流入(由蛋白質激酶C與磷酯酶A2調控)來升高細胞內鈣離子濃度。Nortriptyline是經由與磷酯酶C不相關的內質網鈣離子釋放與蛋白質激酶C敏感的鈣離子流入路徑,來增加鈣離子濃度。另外,低濃度的nortriptyline會促進細胞增生;而高濃度的nortriptyline會造成細胞的凋亡。本論文之結果將有助於了解抗憂鬱藥物對細胞內訊息傳遞系統之影響,且提供了藥物治療作用或臨床副作用一個新的可能藥理作用機轉之思考方向。
Abstract
Depressive disorder is one of the most important diseases influencing human health in the 21st century. Antidepressants can improve some depressive symptoms and signs of depressive disorder in patients. It is thought that neurotransmitters (especially serotonin and/or norepinephrine and/or dopamine) have important roles in antidepression effects, but their pharmacological effects on the intracellular signal transduction pathway remain unclear. The aim of this thesis is to explore the effect of the antidepressants paroxetine (a selective serotonin reuptake inhibitor) and nortriptyline (a tricyclic antidepressant) on the intracellular Ca2+-related signal transduction and apoptosis of human prostate cancer PC3 cells.
By using the fura-2 method, in PC3 cell, we found paroxetine (at concentrations between 10-150 μM) and nortriptyline (at concentrations between 50-500 μM) increased [Ca2+]i of PC3 cells in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+ indicating that Ca2+ entry and release both contributed to the [Ca2+]i rise. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor nearly abolished paroxetine and nortriptyline-induced Ca2+ release. Conversely, pretreatment with nortriptyline greatly reduced the inhibitor-induced [Ca2+]i rise, suggesting that antidepressants released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C with U73122 inhibited paroxetine-induced [Ca2+]i rise by 80%, but did not change nortriptyline-induced [Ca2+]i rise. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators. Nortriptyline-induced Ca2+ influx was inhibited by activation of protein kinase C. Nortriptyline at a concentration of 10 μM increased the viability of the PC3 cells. At 50 μM, nortriptyline killed 45% of the cells, and induced significant apoptosis, as measured by propidium iodide staining.
Collectively, in PC3 cells, paroxetine induced [Ca2+]i rise is caused by phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Nortriptyline increased [Ca2+]i via phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx from the protein kinase C-sensitive pathway. Nortriptyline also induced apoptosis at a higher level. The results of this thesis may be helpful for understanding the effects of antidepressants on the intracellular signaling of cultured cells, and might illustrate a new possible mechanism concerning antidepressants’ therapeutic effects or clinical side effects.
目次 Table of Contents
致謝1
中文摘要2
Abstract.....4
Abbreviations…10
Chapter 1 Introduction…12 1-1 Background..12
1-2 Depressive disorder13
1-3 Antidepressants….18
1-4 Paroxetine.26
1-5 Nortriptyline....27
1-6 Ca2+ signals .….28
1-7 Apoptosis….....32
1-8 Aims and procedures33
Chapter 2 Methods.35
2-1 Cell culture35
2-2 [Ca2+]i measurements…35
2-3 Mn2+ quench of fura-2 fluorescence….36
2-4 Cell viability assays36
2-5 Apoptosis assays…37
2-6 Solutions used in [Ca2+]i measurements38
2-7 Chemicals39
2-8 Statistics..39
Chapter 3 Effect of the antidepressant paroxetine on Ca2+ movement in PC3 human prostate cancer cells..40
3-1 Introduction…40
3-2 Results…41
3-3 Discussion…45
Chapter 4 Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells…49
4-1 Introduction….49
4-2 Results….50
4-3 Discussion.54
Chapter 5 Conclusion…..58
References…....60
Figures.....81
Figure 1-1: The major connections of the stress circuit.…..81
Figure 1-2: Monoamine neurotransmitter regulation of mood and behavior..83
Figure 1-3: Areas of the brain affected by depression….84
Figure 1-4: A hypothesis of the relationship of brain-derived neurotrophic factor (BDNF) to depression and the mechanism of antidepressant..85
Figure 1-5: Chemical structural of nortriptyline.86
Figure 1-6: The mechanism of tricyclic antidepressants.87
Figure 1-7: Chemical structural of paroxetine…88
Figure 3-1: Effect of paroxetine on [Ca2+]i in fura-2-loaded PC3 cells89
Figure 3-2: Effect of removal of Ca2+ on paroxetine-induced [Ca2+]i rise…90
Figure 3-3: Concentration-response plots of paroxetine-induced [Ca2+]i rise….91
Figure 3-4: Effect of paroxetine on Ca2+ influx by measuring Mn2+ quench….92
Figure 3-5: Suppression effect of aristolochic acid, PMA, GF109203X, econozole and SK&F96365 on paroxetine-induced [Ca2+]i rise.….93
Figure 3-6: Intracellular Ca2+ stores of paroxetine-induced Ca2+ release (thapsigargin)…94
Figure 3-7: Intracellular Ca2+ stores of paroxetine-induced Ca2+ release (BHQ)….95
Figure 3-8: Intracellular Ca2+ stores of paroxetine-induced Ca2+ release (CPA)..96
Figure 3-9: In Ca2+-free medium, ATP-induced Ca2+ release in PC3 cells97
Figure 3-10: Effect of U73122 on paroxetine-induced Ca2+ release98
Figure 4-1: Effect of nortriptyline on [Ca2+]i in fura-2-loaded PC3 cells99
Figure 4-2: Effect of removal of Ca2+ on nortriptyline-induced [Ca2+]i rise….100
Figure 4-3: Concentration-response plots of nortriptyline-induced [Ca2+]i rise…101
Figure 4-4: Effect of nortriptyline on Ca2+ influx by measuring Mn2+ quench…102
Figure 4-5: Effect of Ca2+ channel blocker, protein kinase C activator and inhibitor, and protein kinase A inhibitor on nortriptyline-induced [Ca2+]i rise..103
Figure 4-6: Effect of nortriptyline on thapsigargin-induced passive depleting of endoplasmic reticulum Ca2+ store in PC3 cells104
Figure 4-7: Effect of thapsigargin on nortriptyline-induced Ca2+ release in PC3 cells…105
Figure 4-8: Effect of ATP on [Ca2+]i in PC3 cells106
Figure 4-9: Effect of U73122 on nortriptyline-induced Ca2+ release…..107
Figure 4-10: The effect of nortriptyline on the viability of PC3 cells..108
Figure 4-11: The effect of nortriptyline on apoptosis of PC3 cells109
Figure 5-1: The mechanism of paroxetine induced [Ca2+]i rise in PC3 cells.110
Figure 5-2: The mechanism of nortriptyline induced [Ca2+]i rise in PC3 cells111
Figure 5-3: Effect of nortriptyline on the viability and apoptosis of PC3 cells…..112
Publications and Presentations.113
Appendix 1: Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells. (2010) Drug Development Research 71:323-330…115
Appendix 2: Effect of the antidepressant paroxetine on Ca2+ movement in PC3 human prostate cancer cells. (2010) Drug Development Research 71:120-126…123
Appendix 3: Association analysis of the COMT/MTHFR genes and geriatric depression: An MRI study of putamen. (2009) International Journal of Geriatric Psychiatry 24:847-855..…..130
參考文獻 References
(1) Abela JR, D’Alessandro DU. (2002) Beck’s cognitive therapy of depression: a test of the diathesis-stress and causal mediation components. Br J Clin Psychol 41: 111-128.
(2) Albert AP, Large WA. (2002) Activation of store-operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes. J Physiol 544: 113–125.
(3) Amrein R, Hetzel W, Stabl M, Schmid-Burgk W. (1993) RIMA--a new concept in the treatment of depression with moclobemide. Int Clin Psychopharmacol 7: 123-132.
(4) Anderson IM. (2000) Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 58: 19-36.
(5) Andreasen NC, Swayze V 2nd, Flaum M, Alliger R, Cohen G. (1990) Ventricular abnormalities in affective disorder: clinical and demographic correlates. Am J Psychiatry 147: 893-900.
(6) Andreescu C, Butters MA, Begley A, Rajji T, Wu M, Meltzer CC, Reynolds CF 3rd, Aizenstein H. (2008) Gray matter changes in late life depression—a structural MRI analysis. Neuropsychopharmacology 33: 2566-2572.
(7) Anttila SA, Leinonen EV. (2001) A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 7: 249-264.
(8)Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E. (1995) Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 56: 395-401.
(9) Basset O, Boittin FX, Cognard C, Constantin B, Ruegg UT. (2006) Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes. Biochem J 395: 267-276.
(10) Becker B, Morel N, Vanbellinghen AM, Lebrun P. (2004) Blockade of calcium entry in smooth muscle cells by the antidepressant imipramine. Biochem Pharmacol 68: 833-842.
(11) Belmaker RH, Agam G. (2008) Major depressive disorder. N Engl J Med 358: 55-68.
(12) Berridge MJ, Bootman MD, Roderick HL. (2003) Calcium signaling: dynamics, homeostasis and remodeling. Nat Rev Mol Cell Biol 4: 517-529.
(13) Berridge MJ. (2002) The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32: 235-249.
(14) Berridge MJ. (1997) Elementary and global aspects of calcium signaling. J Exp Biol 200: 315-319.
(15) Berridge MJ. (1995) Inositol trisphosphate and calcium signaling. Ann N Y Acad Sci 766: 31-43.
(16) Beyer JL, Krishnan KR. (2002) Volumetric brain imaging findings in mood disorders. Bipolar Disord 4: 89-104.
(17) Blackwell B. (1963) Hypertensive crisis due to monoamine-oxidase inhibitors. Lancet 2: 849-850.
(18) Blaustein MP. (1988) Calcium transport and buffering in neurons. Trends Neurosci 11: 438-443.
(19) Boittin FX, Gribi F, Serir K, Be′ny JL. (2008) Ca2+-independent PLA2 controls endothelial store-operated Ca2+ entry and vascular tone in intact aorta. Am J Physiol Heart Circ Physiol 295: H2466–H2474.
(20) Boittin FX, Petermann O, Hirn C,Mittaud P, Dorchies OM, Roulet E, Ruegg UT. (2006) Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers. J Cell Sci 119: 3733–3742.
(21) Bootman MD, Berridge MJ, Roderick HL. (2002) Calcium signalling: more messengers, more channels, more complexity. Curr Biol 12: R563–R565.
(22) Brini M, Manni S, Carafoli E. (2002) A study of the activity of the plasma membrane Na/Ca exchanger in the cellular environment. Ann N Y Acad Sci 976: 376-381.
(23) Bukh JD, Bock C, Vinberg M, Werge T, Gether U, Vedel Kessing L. (2009) Interaction between genetic polymorphisms and stressful life events in first episode depression. J Affect Disord 119: 107-115.
(24) Celano E, Tiraboschi E, Consogno E, D'Urso G, Mbakop MP, Gennarelli M, de Bartolomeis A, Racagni G, Popoli M. (2003) Selective regulation of presynaptic calcium/calmodulin-dependent protein kinase II by psychotropic drugs. Biol Psychiatry 53: 442-429.
(25) Chang HC, Cheng HH, Huang CJ, Chen WC, Chen IS, Liu SI, Hsu SS, Chang HT, Wang JK, Lu YC, Chou CT, Jan CR. (2006) Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells. J Recept Signal Transduct Res 26: 199–212.
(26) Chang HC, Huang CC, Huang CJ, Cheng JS, Liu SI, Tsai JY, Chang HT, Huang JK, Chou CT, Jan CR. (2008) Desipramine induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation. Toxicology 250: 9–14.
(27) Charriaut-Marlangue C. (2004) Apoptosis: a target for neuroprotection. Therapie 59: 185-190.
(28) Chen WC, Huang CC, Huang CJ, Chien JM, Lin KL, Lu YC, Chen IS, Liu SI, Hsu SS, Chang HT, Chou CT, Jan CR. (2008) Mechanism of paroxetine-induced cell death in renal tubular cells. Basic Clin Pharmacol Toxicol 103: 407–413.
(29) Cheng HH, Huang CJ, Chen WC, Chen IS, Liu SI, Hsu SS, Chang HT, Wang JK, Lu YC, Jan CR. (2006) Effect of nortriptyline on intracellular Ca2+ handling and viability in canine renal tubular cells. Chin J Physiol 49: 283-289.
(30) Chou CT, He S, Jan CR. (2007) Paroxetine-induced apoptosis in human osteosarcoma cells: Activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. Toxicol Appl Pharmacol 218: 265-273.
(31) Clapham DE. (1995) Intracellular calcium. Replenishing the stores. Nature 375: 634–635.
(32) Coffey CE, Wilkinson WE, Weiner RD, Parashos IA, Djang WT, Webb MC, Figiel GS, Spritzer CE. (1993) Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch Gen Psychiatry 50: 7-16.
(33) Cohen JE, Fields RD. (2004) Extracellular calcium depletion in synaptic transmission. Neuroscientist 10: 12-17.
(34) Danileviiute V, Sveikata A, Adomaitiene V, Gumbrevicius G, Fokas V, Sveikatiene R. (2009) Efficacy, tolerability, and preference of mirtazapine orally disintegrating tablets in depressed patients: a 17-week naturalistic study in Lithuania. Medicina (Kaunas) 45: 778-784.
(35) DasGupta K. (1998) Treatment of depression in elderly patients: recent advances. Arch Fam Med 7: 274-280.
(36) de Boer T. (1996) The pharmacologic profile of mirtazapine. J Clin Psychiatry Supple 4: 19-25.
(37) Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT. (2007) Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain 8: 315–324.
(38) Drzyzga LR, Marcinowska A, Obuchowicz E. (2009) Antiapoptotic and neurotrophic effects of antidepressants: a review of clinical and experimental studies. Brain Res Bull 79: 248-257.
(39) Duval F, Mokrani MC, Crocq MA, Bailey P, Macher JP. (1994) Influence of thyroid hormones on morning and evening TSH response to TRH in major depression. Biol Psychiatry 35: 926-934.
(40) Fava M, Rush AJ, Wisniewski SR, Nierenberg AA, Alpert JE, McGrath PJ, Thase ME, Warden D, Biggs M, Luther JF, Niederehe G, Ritz L, Trivedi MH. (2006) A comparison of mirtazapine and nortriptyline following tow consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry 163: 1161-1172.
(41) Fleishaker JC. (2000) Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. Clin Pharmacokinet 39: 413-427.
(42) Florenzano F, Viscomi MT, Mercaldo V, Longone P, Bernardi G, Bagni C, Molinari M, Carrive P. (2006) P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons. J Com Neurol 498: 58–67.
(43) Fossati P, Radtchenko A, Boyer P. (2004) Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol 14 suppl 5: S503-510.
(44) Franssen EJ, Kunst PW, Bet PM, Strack van Schijndel RJ, van Loenen AC, Wilhelm AJ. (2003) Toxicokinetics of nortriptyline and amitriptyline: two case reports. Ther Drug Monit 25: 248–251.
(45) Fuchs E, Czeh B, Kole MH, Michaelis T, Lucassen PJ. (2004) Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol suppl 5: S481-490.
(46) Furutani K, Ohno Y, Inanobe A, Hibino H, Kurachi Y. (2009) Mutational and in silico analyses for antidepressant block of astroglial inward-rectifier Kir4.1 channel. Mol Pharmacol 75: 1287-1295.
(47) Ganitkevich VY. (2003) The role of mitochondria in cytoplasmic Ca2+ cycling. Exp Physiol 88: 91-97.
(48) Gil-Ad I, Zolokov A, Lomnitski L, Taler M, Bar M, Luria D, Ram E, Weizman A. (2008) Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice. Int J Oncol 33: 277–286.
(49) Gillman PK. (2007) Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 151: 737-748.
(50) Ginsberg LD. (2009) Impact of drug tolerability on the selection of antidepressant treatment in patients with major depressive disorder. CNS Spectr 14: 8-14.
(51) Gomperts BD, Tatham PER, Kramer IM. (2002) Chapter 7: Calcium and signal transduction. Signal Transduction (AP/Elsevier): p145-169. ISBN: 0-1228-9631-9
(52) Grynkiewicz G, Poenie M, Tsien RY. (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450.
(53) Gunasekara NS, Noble S, Benfield P. (1998) Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders. Drugs 55: 85-120.
(54) Haller T, Dietl P, Deetjen P, Volkl H. (1996) The lysosomal compartment as intracellular calcium store in MDCK cells: a possible involvement in InsP3-mediated Ca2+ release. Cell Calcium 19: 157-165.
(55) Hammen C, Kim EY, Eberhart NK, Brennan PA. (2009) Chronic and acute stress and the prediction of major depression in women. Depress Anxiety 26: 718-723.
(56) Hayes PE, Kristoff CA. (1986) Adverse reactions to five new antidepressants. Clin Pharm 5: 471-480.
(57) Heath-Engel HM, Chang NC, Shore GC. (2008) The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene 27: 6419-6433.
(58) Helmeste DM, Tang SW. (1998) The role of calcium in the etiology of the affective disorders. Jpn J Pharmacol 77: 107-116.
(59) Henshall DC. (2007) Apoptosis signaling pathways in seizure-induced neuronal death and epilepsy. Biochem Soc Trans 35: 421-423.
(60) Herrington J, Park YB, Babcock DF, Hille B. (1996) Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells. Neuron 16: 219-228.
(61) Herrmann LL, Masurier ML, Ebmeier KP. (2008) White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 79: 619-624.
(62) Hofmann PJ, Nutzinger DO, Kotter MR, Herzog G. (2001) The hypothalamic-pituitary-thyroid axis in agoraphobia, panic disorder, major depression and normal controls. J Affect Disord 66: 75-77.
(63) Hollister LE. (1981) Current antidepressant drugs: their clinical use. Drugs 22: 129-152.
(64) Hsu SS, Huang CJ, Chen JS, Cheng HH, Chang HT, Jiann BP, Lin KL, Wang JL, Ho CM, Jan CR. (2004) Effect of nortriptyline on intracellular Ca2+ handling and proliferation in human osteosarcoma cells. Basic Clin Pharmacol Toxicol 95: 24-130.
(65) Huang CJ, Cheng HH, Chou CT, Kuo CC, Lu YC, Tseng LL, Chu ST, Hsu SS, Wang JL, Lin KL, Chen IS, Liu SI, Jan CR. (2007) Desipramine-induced Ca2+ movement and cytotoxicity in PC3 human prostate cancer cells. Toxicol In Vitro 21: 449-456.
(66) Huang JK, Cheng HH, Huang CJ, Kuo CC, Chen WC, Liu SI, Hsu SS, Chang HT, Lu YC, Tseng LL, Chiang AJ, Chou CT, Jan CR. (2006) Effect of capsazepine on cytosolic Ca2+ levels and proliferation of human prostate cancer cells. Toxicol In Vitro 20: 567–574.
(67) Huang JK, Huang CC, Lu T, Chang HT, Lin KL, Tsai JY, Liao WC, Chien JM, Jan CR. (2009) Effect of MK-886 on Ca2+ level and viability in PC3 human prostate cancer cells. Basic Clin Pharmacol Toxicol 104: 441-447.
(68) Huang JK, Liu CS, Chou CT, Liu SI, Hsu SS, Chang HT, Hsieh CH, Chang CH, Chen WC, Jan CR. (2005) Effects of econazole on Ca2+ levels in and the growth of human prostate cancer PC3 cells. Clin Exp Pharmacol Physiol 32: 735–741.
(69) Hughes JR, Stead LF, Lancaster T. (2003) Antidepressants for smoking cessation. Cochrane Database Syst Rev 2: CD000031.
(70) Husain MM, McDonald WM, Doraiswamy PM, Figiel GS, Na C, Escalona PR, Boyko OB, Nemeroff CB, Krishnan KR. (1991) A magnetic resonance imaging study of putamen nuclei in major depression. Psychiatry Res 40: 95-99.
(71) Hu XH, Bull SA, Hunkeler EM, Ming E, Lee JY, Fireman B, Markson LE. (2004) Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry 65: 959-965.
(72) Ishikawa J, Ohga K, Yoshino T, Takezawa R, Ichikawa A, Kubota H, Yamada T. (2003) A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes. J Immunol 170: 4441–4449.
(73) Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K. (1996) A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull 19: 1518-1520.
(74) Jan CR, Lu YC, Tseng LL, Jiann BP, Chang HT, Wang JL, Chen WC, Huang JK. (2003) Effect of the antidepressant desipramine on cytosolic Ca2+ movement and proliferation in human osteosarcoma cells. Pharmacology 69: 190-196.
(75) Jarskog LF, Selinger ES, Lieberman JA, Gilmore JH. (2004) Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry 161: 109-115.
(76) Jiang N, Zhang ZM, Liu L, Zhang C, Zhang YL, Zhang ZC. (2006) Effects of Ca2+ channel blockers on store-operated Ca2+ channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats. World J Gastroenterol 12: 4694–4698.
(77) Johnson JG, Cohen P, Kasen S, Brook JS. (2005) Personality disorder traits associated with risk for unipolar depression during middle adulthood. Psychiatry Res 136: 113-121.
(78) Joshi PG, Singh A, Ravichandra B. (1999) High concentrations of tricyclic antidepressants increase intracellular Ca2+ in cultured neural cells. Neurochem Res 24: 391-398.
(79) Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 17: 16-23.
(80) Kamath M, Finkel SI, Moran MB. (1996) A retrospective chart review of antidepressant use, effectiveness, and adverse effects in adults age 70 and older. Am J Geriatr Psychiatry 4: 167-172.
(81) Katzman MA. (2009) Current considerations in the treatment of generalized anxiety disorder. CNS Drugs 23: 103-120.
(82) Keilhoff G, Becker A, Grecksch G, Bernstein HG, Wolf G. (2006) Cell proliferation is influenced by bulbectomy and normalized by imipramine treatment in a region-specific manner. Neuropsychopharmacology 31: 1165-1176.
(83) Kent JM. (2000) SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. Lancet 355: 911-918.
(84) Kobayashi T, Washiyama K, Ikeda K. (2006) Inhibition of G protein activated inwardly rectifying K+ channels by the antidepressant paroxetine. J Pharmacol Sci 102: 278–287.
(85) Korchak HM, Corkey BE, Yaney GC, Kilpatrick LE. (2001) Negative regulation of ligand-initiated Ca2+ uptake by PKC-beta II in differentiated HL60 cells. Am J Physiol Cell Physiol 281: C514–C523.
(86) Krishnan KR, McDonald WM, Escalona PR, Doraiswamy PM, Na C, Husain MM Figiel GS, Boyko OB, Ellinwood EH, Nemeroff CB. (1992) Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. Arch Gen Psychiatry 49: 553-557.
(87) Large WA, Saleh SN, Albert AP. (2009) Role of phosphoinositol 4,5-bisphosphate and diacylglycerol in regulating native TRPC channel proteins in vascular smooth muscle. Cell Calcium 45: 574-582.
(88) Lazary J, Juhasz G, Anderson IM, Jacob CP, Nguyen TT, Lesch KP, Reif A, Deakin JF, Bagdy G. (2010) Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. Eur neuropsychopharmacol [Epub ahead of print].
(89) Lesch KP. (2004) Gene-environment interaction and the genetics of depression. J Psychiatry Neurosci 29: 174-184.
(90) Levkovitz Y, Gil-Ad I, Zeldich E, Dayag M, Weizman A. (2005) Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci 27: 29-42.
(91) Liao J, Schneider A, Datta NS, McCauley LK. (2006) Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66: 9065–9073.
(92) Lin HF, Kuo YT, Chiang IC, Chen HM, Chen CS. (2005) Structural abnormality on brain magnetic resonance imaging in late-onset major depressive disorder. Kaohsiung J Med Sci 21: 405-411.
(93) Li N, Lin P, Cai C, Pan Z, Weisleder N, Ma J. (2009) The aminoterminal peptide of Bax perturbs intracellular Ca2+ homeostasis to enhance apoptosis in prostate cancer cells. Am J Physiol Cell Physiol 296: C267–C272.
(94) Lirk P, Haller I, Hausott B, Ingorokva S, Deibl M, Gerner P, Klimaschewski L. (2006) The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity. Anesth Analg 102: 1728-1733.
(95) Li YF, Luo ZP. (2002) Desipramine antagonized corticosterone-induced apoptosis in cultured PC12 cells. Acta Pharmacol Sin 23: 311-314.
(96) Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. (2000) Chapter 21: Nerve cells. Molecular Cell Biology, 4th edition. W.H. Freeman and Company: p911-967. ISBN: 0-7167-3136-3
(97) Lopez JF, Akil H, Watson SJ. (1999) Neural circuits mediating stress. Biol Psychiatry 46: 1461-1471.
(98) Lovborg H, Gullbo J, Larsson R. (2005) Screening for apoptosis--classical and emerging techniques. Anticancer Drugs 16: 593-599.
(99) Lucassen PJ, Fuchs E, Czeh B. (2004) Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 55: 789-796.
(100) Lueboonthavatchai P. (2009) Role of stress areas, stress severity, and stressful life events on the onset of depressive disorder: a case-control study. J Med Assoc Thai 92: 1240-1249.
(101) Lupescu A, Bock CT, Lang PA, Aberle S, Kaiser H, Kandolf R, Lang F. (2006) Phospholipase A2 activity-dependent stimulation of Ca2+ entry by human parvovirus B19 capsid protein VP1. J Virol 80: 11370–11380.
(102) Ma R, Pluznick J, Kudlacek P, Sansom SC. (2001) Protein kinase C activates store-operated Ca2+ channels in human glomerular mesangial cells. J Biol Chem 276: 25759–25765.
(103) Majeroni BA, Hess A. (1998) The pharmacologic treatment of depression. J Am Board Fam Pract 11: 127-139.
(104) Marks DM, Park MH, Ham BJ, Han C, Patkar AA, Masand PS, Pae CU. (2008) Paroxetine: safety and tolerability issues. Expert Opin Drug Saf 7: 783–794.
(105) Masand PS, Gupta S. (1999) Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry 7: 69-84.
(106) Mattson MP, Keller JN, Begley JG. (1998) Evidence for synaptic apoptosis. Exp Neurol 153: 35-48.
(107) McFadzean I, Gibson A. (2002) The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 135: 1-13.
(108) McPherson PS, Campbell KP. (1993) Characterization of the major brain form of the ryanodine receptor/Ca2+ release channel. J Biol Chem 268: 19785-19790.
(109) Melero A, Garrigues TM, Alós M, Kostka KH, Lehr CM, Schaefer UF. (2009) Nortriptyline for smoking cessation: release and human skin diffusion from patches. Int J Pharm 378: 101-107.
(110) Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, Bienfait K, Dicke A. (2009) The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson’s disease. Mov Disord 24: 1325-1332.
(111) Merritt JE, Jacob R, Hallam TJ. (1989) Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem 264: 1522-1527.
(112) Monteleone P. (2001) Endocrine disturbances and psychiatric disorders. Current Opinion in Psychiatry 14: 605-610.
(113) Mosing MA, Gordon SD, Medland SE, Statham DJ, Nelson EC, Heath AC, Martin NG, Wray NR. (2009) Genetic and environmental influences on the comorbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study. Depress Anxiety 26: 1004-1011.
(114) Muraoka S, Kamei K, Muneoka K, Takigawa M. (1998) Chronic imipramine administration amplifies the serotonin2A receptor-induced intracellular Ca2+ mobilization in C6 glioma cells through a calmodulin-dependent pathway. J Neurochem 71: 1709-1718.
(115) Nagata K, Imai T, Yamashita T, Tsuda M, Tozaki-Saitoh H, Inoue K. (2009) Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain 5: 20.
(116) Nair NP, Ahmed SK, Kin NM. (1993) Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide. J Psychiatry Neurosci 18: 214-225.
(117) Nicotera TM, Schuster DP, Bourhim M, Chadha K, Klaich G, Corral DA. (2009) Regulation of PSA secretion and survival signaling by calcium-independent phospholipase A2-beta in prostate cancer cells. Prostate 69: 1270-1280.
(118) Nutt DJ. (2008) Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry 69 Suppl E1: 4-7.
(119) Overmier JB, Seligman ME. (1967) Effects of inescapable shock upon subsequent escape and avoidance responding. J Comp Physiol Psychol 63: 28-33.
(120) Pan CC, McQuoid DR, Taylor WD, Payne ME, Ashley-Koch A, Steffens DC. (2009) Association analysis of the COMT/MTHFR genes and geriatric depression: An MRI study of putamen. Int J Geriatr Psychiatry 24: 847-855.
(121) Ploppa A, Ayers DM, Johannes T, Unertl KE, Durieux ME. (2008) The inhibition of human neutrophil phagocytosis and oxidative burst by tricyclic antidepressants. Anesth Analg 107: 1229-1235.
(122) Popoli M, Brunello N, Perez J, Racagni G. (2000) Second messenger-regulated protein kinases in the brain: their functional role and the action of antidepressant drugs. J Neurochem 74: 21-33.
(123) Post A, Crochemore C, Uhr M, Holsboer F, Behl C. (2000) Differential induction of NF-kappaB activity and neural cell death by antidepressants in vitro. Eur J Neurosci 12: 4331-4337.
(124) Prevarskaya N, Skryma R, Bidaux G, Flourakis M, Shuba Y. (2007) Ion channels in death and differentiation of prostate cancer cells. Cell Death Differ 14: 1295-1304.
(125) Punay NC, Couch JR. (2003) Antidepressants in the treatment of migraine headache. Curr Pain Headache Rep 7: 51-54.
(126) Putney Jr JW. (1986) A model for receptor-regulated calcium entry. Cell Calcium 7: 1–12.
(127) Quinn T, Molloy M, Smyth A, Baird AW. (2004) Capacitative calcium entry in guinea pig gallbladder smooth muscle in vitro. Life Sci 74: 1659–1669.
(128) Radden J. (2003) Is this dame melancholy?: equating today’s depression and past melancholia. Philosophy Psychiatry Psychology 10: 37-52.
(129) Redrobe JP, Bourin M, Colombel MC, Baker GB. (1998) Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity. Psychopharmacology (Berl) 138: 1-8.
(130) Remick RA, Froese C, Keller FD. (1989) Common side effects associated with monoamine oxidase inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 13: 497-504.
(131) Ressler KJ, Nemeroff CB. (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety Suppl 1: 2-19.
(132) Rizzuto R, Marchi S, Bonora M, Aguiari P, Bononi A, De Stefani D, Giorgi C, Leo S, Rimessi A, Siviero R, Zecchini E, Pinton P. (2009) Ca2+ transfer from the ER to mitochondria: when, how and why. Biochim Biophys Acta 1787: 1342-1351.
(133) Robinson MJ, Edwards SE, Iyengar S, Bymaster F, Clark M, Katon W. (2009) Depression and pain. Front Biosci 14: 5031-5051.
(134) Robinson RG. (2003) Poststroke depression: prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 54: 376-387.
(135) Rojo-Moreno L, Livianos-Aldana L, Cervera-Martinez G, Dominguez-Carabantes JA, Reig-Cebrian MJ. (2002) The role of stress in the onset of depressive disorders. A controlled study in a Spanish clinical sample. Soc Psychiatry Psychiatr Epidemiol 37: 592-598.
(136) Rosetti M, Frasnelli M, Tesei A, Zoli W, Conti M. (2006) Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells. J Exp Ther Oncol 6: 23–29.
(137) Rouzaire-Dubois B, Dubois JM. (2004) Calcium-dependent proliferation of NG108-15 neuroblastoma cells. Gen Physiol Biophys 23: 231-239.
(138) Sadock BJ, Sadock VA. (2000) Chapter 14: Mood disorder. Comprehensive Textbook of Psychiatry, 7th edition. Lippincott Williams & Wilkins: p1284-1440. ISBN: 0-683-30128-4.
(139) Sadock BJ, Sadock VA. (2007) Chapter 36: Biological therapies. Synopsis of Psychiatry, 10th edition. Lippincott Williams & Wilkins: p976-1126. ISBN: 978-0-7817-7327-0.
(140) Saidak Z, Mentaverri R, Brown EM. (2009) The role of the calcium-sensing receptor in the development and progression of cancer. Endocr Rev 30: 178-195.
(141) Sairanen M, Lucas G, Ernfors P, Castren M, Castren E. (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25: 1089-1094.
(142) Saleh SN, Albert AP, Peppiatt-Wildman CM, Large WA. (2008) Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes. J Physiol 586: 2463–2476.
(143) Seligman ME, Maier SF. (1967) Failure to escape traumatic shock. J Exp Psychol 74: 1-9.
(144) Sen S, Duman R, Sanacora G. (2008) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 64: 527-532.
(145) Settle EC Jr. (1998) Bupropion sustained release: side effect profile. J Clin Psychiatry. Suppl 4: 32-36
(146) Shabbir M, Ryten M, Thompson C, Mikhailidis D, Burnstock G. (2008) Characterization of calcium-independent purinergic receptor-mediated apoptosis in hormone-refractory prostate cancer. BJU Int 101: 352-359.
(147) Shabnam GN, Th C, Kho D, Ce RHC. (2003) Therapies for depression in Parkinson's disease. Cochrane Database Syst Rev 3: CD003465.
(148) Shideman CR, Reinardy JL, Thayer SA. (2009) gamma-Secretase activity modulates store-operated Ca2+ entry into rat sensory neurons. Neurosci Lett 451: 124–128.
(149) Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA. (2002) Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos 30: 1102-1107.
(150) Singaravelu K, Lohr C, Deitmer JW. (2008) Calcium-independent phospholipase A2 mediates store-operated calcium entry in rat cerebellar granule cells. Cerebellum 7: 467–481.
(151) Smani T, Patel T, Bolotina VM. (2008) Complex regulation of store-operated Ca2+ entry pathway by PKC-epsilon in vascular SMCs. Am J Physiol Cell Physiol 294: C1499-1508.
(152) Stahl SM, Grady MM, Moret C, Briley M. (2005) SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 10: 732-747.
(153) Stahl SM. (2009) Mechanism of action of trazodone: a multifunctional drug. CNS Spectr 14: 536-546.
(154) Sterner EY, Kalynchuk LE. (2010) Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Prog Neuropsychopharmacol Biol Psychiatry 34: 777-790.
(155) Strumper D, Durieux ME, Hollmann MW, Troster B, den Bakker CG, Marcus MA. (2003) Effects of antidepressants on function and viability of human neutrophils. Anesthesiology 98: 1356-1362.
(156) Su S, Ohno Y, Lossin C, Hibino H, Inanobe A, Kurachi Y. (2007) Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline. J Pharmacol Exp Ther 320: 573-580.
(157) Takebayashi M, Kagaya A, Inagaki M, Kozuru T, Jitsuiki H, Kurata K, Okamoto Y, Yamawaki S. (2000) Effects of antidepressants on gamma-aminobutyric acid- and N-methyl-D-aspartate-induced intracellular Ca2+ concentration increases in primary cultured rat cortical neurons. Neuropsychobiology 42: 120-126.
(158) Tang KY, Lu T, Chang CH, Lo YK, Cheng JS, Wang JL, Chang HT, Jan CR. (2001) Effect of fluoxetine on intracellular Ca2+ levels in bladder female transitional carcinoma (BFTC) cells. Pharmacol Res 43: 503-508.
(159) Tang SW, Helmeste D. (2008) Paroxetine. Expert Opin Pharmacother 9: 787–794.
(160) Tedesco E, Rigoni M, Caccin P, Grishin E, Rossetto O, Montecucco C. (2009) Calcium overload in nerve terminals of cultured neurons intoxicated by alpha-latrotoxin and snake PLA2 neurotoxins. Toxicon 54: 138-144.
(161) Terstappen GC, Pula G, Carignani C, Chen MX, Roncarati R. (2001) Pharmacological characterization of the human small conductance calcium-activated potassium channel hSK3 reveals sensitivity to tricyclic antidepressants and antipsychotic phenothiazines. Neuropharmacology 40: 772-783.
(162) Thase ME. (2006) Depression and sleep: pathophysiology and treatment. Dialogues Clin Neurosci 8: 217-226.
(163) Thastrup O, Cullen PJ, Drobak BK, Hanley MR, Dawson AP. (1990) Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Pro Natl Acad Sci USA 87: 2466–2470.
(164) Thompson AK, Mostafapour SP, Denlinger LC, Bleasdale JE, Fisher SK. (1991) The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation. J Biol Chem 266: 23856–23862.
(165) Tomiyoshi R, Kamei K, Muraoka S, Muneoka K, Takigawa M. (1999) Serotonin-induced platelet intracellular Ca2+ responses in untreated depressed patients and imipramine responders in remission. Biol Psychiatry 45: 1042-1048.
(166) Tsien RY. (1980) New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry 19: 2396-2404.
(167) Turvey MR, Wang Y, Gu Y. (2010) The effects of extracellular nucleotides on [Ca2+]i signaling in a human-derived renal proximal tubular cell line (HKC-8). J Cell Biochem 109: 132-139.
(168) Uchitomi Y, Kugaya A, Akechi T, Nakano T, Wenner M, Okamura H, Takebayashi M, Kagaya A, Saeki T, Yamawaki S. (2001) Three sets of diagnostic criteria for major depression and correlations with serotonin-induced platelet calcium mobilization in cancer patients. Psychopharmacology (Berl) 153: 244-248.
(169) Venkatachalam K, van Rossum DB, Patterson RL, Ma HT, Gill DL. (2002) The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 4: E263-272.
(170) Wahlstrom A, Lenhammar L, Ask B, Rane A. (1994) Tricyclic antidepressants inhibit opioid receptor binding in human brain and hepatic morphine glucuronidation. Pharmacol Toxicol 75: 23-27.
(171) Wang GK, Mitchell J, Wang SY. (2008) Block of persistent late Na+ currents by antidepressant sertraline and paroxetine. J Membr Biol 222: 79–90.
(172) Wassenberg JJ, Clark KD, Nelson DL. (1997) Effect of SERCA pump inhibitors on chemoresponses in Paramecium. J Eukaryot Microbiol 44: 574–581.
(173) Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann, Lunde I. (1986) Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorder. Arch Gen Psychiatry 43: 923-929.
(174) Wichers M, Schrijvers D, Geschwind N, Jacobs N, Myin-Germeys I, Thiery E, Derom C, Sabbe B, Peeters F, Delespaul P, van Os J. (2009) Mechanisms of gene-environment interactions in depression: evidence that genes potentiate multiple sourced of adversity. Psychol Med 39: 1077-1086.
(175) Wilens TE, Biederman J, Geist DE, Steingard R, Spencer T. (1993) Nortriptyline in the treatment of ADHD: a chart review of 58 cases. J Am Child Adolesc Psychiatry 32: 343-349.
(176) Wong DT, Bymaster FP, Engleman EA. (1995) Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci 57: 411-441
(177) Xia Z, Bergstrand A, DePierre JW, Nassberger L. (1999) The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol 13: 338-347.
(178) Yamawaki S, Kagaya A, Tawara Y, Inagaki M. (1998) Intracellular calcium signaling systems in the pathophysiology of affective disorders. Life Sci 62: 1665-1670.
(179) Zubenko GS, Maher B, Hughes HB 3rd, Zubenko WN, Stiffler JS, Kaplan BB, Marazita ML. (2003) Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 123B: 1-18.
電子全文 Fulltext
本電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。
論文使用權限 Thesis access permission:校內校外均不公開 not available
開放時間 Available:
校內 Campus:永不公開 not available
校外 Off-campus:永不公開 not available

您的 IP(校外) 位址是 34.234.83.135
論文開放下載的時間是 校外不公開

Your IP address is 34.234.83.135
This thesis will be available to you on Indicate off-campus access is not available.

紙本論文 Printed copies
紙本論文的公開資訊在102學年度以後相對較為完整。如果需要查詢101學年度以前的紙本論文公開資訊,請聯繫圖資處紙本論文服務櫃台。如有不便之處敬請見諒。
開放時間 available 已公開 available

QR Code