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博碩士論文 etd-0621102-162054 詳細資訊
Title page for etd-0621102-162054
論文名稱
Title
一氧化碳、腺苷及麩氨酸在大鼠孤立束核內心臟血管作用之研究
Cardiovascular Effects of Carbon Monoxide, Adenosine and Glutamate in the Nucleus Tractus Solitarii of Rats
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
85
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
2002-06-12
繳交日期
Date of Submission
2002-06-21
關鍵字
Keywords
孤立束核、一氧化碳、腺苷、麩氨酸
glutamate, adenosine, nucleus tractus solitarii, carbon monoxide
統計
Statistics
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The thesis/dissertation has been browsed 5669 times, has been downloaded 4294 times.
中文摘要
一氧化碳(carbon monoxide, CO)在腦中被認為是一內生性的生物訊息分子。原血紅素氧化酶(heme oxygenase, HO)分解原血紅質(heme)而產生一氧化碳與膽綠素。在腦中,一氧化碳為一神經傳導物質與神經元的訊息分子。我們過去曾發現一氧化碳參與了中樞心臟血管調控作用與感壓反射的作用,而且許多研究指出一氧化碳會影響麩氨酸的神經傳導作用,進一步的研究則發現活化 metabotropic 麩氨酸接受器(metabotropic glutamate receptors, mGluRs)與原血紅素氧化
Abstract
Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and biliverdin. CO has been shown to act as a neurotransmitter and neuronal messenger in the brain. We reported recently that CO was involved in central cardiovascular regulation, modulated the baroreflex, may affect glutamatergic neurotransmission, and metabotropic glutamate receptors (mGluRs) may be coupled to the activation of HO in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine can increase the release of glutamate in the NTS. The present study was designed to investigate the possible interaction of CO, adenosine, and mGluRs groups in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of ascending doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by HO to yield CO, produced decreases in blood pressure and heart rate dose-dependently. In addition, similar cardiovascular effects were observed in adenosine (2.3 nmol) and several agonists for mGluRs groups such as DHPG (group Ⅰ) (0.03 nmol), APDC (group Ⅱ) (0.3 nmol)and L-AP4 (group Ⅲ) (0.3 nmol). These cardiovascular effects of hemin were attenuatd by prior administration of the adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, pre-treatment of HO inhibitor ZnPPⅨ or ZnDPBG (1 nmol) also attenuated the depressor and bradycadic effects of adenosine. Among the mGluRs agonists, prior administration of ZnPPⅨ (1 nmol), an inhibitor of HO activity, significantly attenuated the cardiovascular effects of APDC and L-AP4, and failed to prevent the cardiovascular responses of DHPG. These results indicated an interaction between CO and adenosine, and group Ⅱ and Ⅲ mGluRs may be coupled to the activation of HO in central cardiovascular regulation.




目次 Table of Contents
序言....................1
材料與方法.................17
結果....................26
討論....................33
結論....................39
參考文獻..................40
表.....................51
圖.....................52
參考文獻 References
Barraco RA, Janusz CJ, Polasek PM, Parizon M, Roberts PA. Cardiovascular effects of microinjection of adenosine into the nucleus tractus solitarius. Brain Res Bull. 1988;20:129-132.

Berne RM, Rubio R, Curnish RR. Release of adenosine from ischemic brain. Effect on cerebral vascular resistance and incorporation into cerebral adenine nucleotides, Circ. Res. 1974;35:262-271.

Bisserbe JC, Deckert J, Marangos P. Autoradiographic localization of adenosine uptake sites in guinea pig brain using [3H]dipyridamole. Neurosci Lett. 1986;66:341-345.

Chalmers J, Arnolda L, Kapoor V, Llewellyn-Smith I, Minson J, Pilowsky P. Amino acid neurotransmitters in the central control of blood pressure and in experimental hypertension. J Hypertens Suppl. 1992;10:S27-37.

Christodoulides N, Durante W, Kroll MH, Schafer AI. Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide. Circulation. 1995;91:2306-2309.

Coney AM, Marshall JM. Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia. J Physiol. 1998;509:507-18.


Daly JW, Bruns RF, Snyder SH. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sci. 1981;28:2083-2097.

Daly JW, Padgett W, Shamim MT, Butts-Lamb P, Waters J. 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors. J Med Chem. 1985;28:487-492.

de Jong W, Zandberg P, Bohus B. Central inhibitory noradrenergic cardiovascular control. Prog Brain Res. 1975;42:285-298.

Dirnagl U, Niwa K, Lindauer U, Villringer A. Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. Am J Physiol. 1994;267:H296-301.

Drury AN, Szent-Gyorgyi A. The physiological activity of adenosine compounds with especial reference to their action upon the mammalian heart. J Physiol Lond. 1929; 68:213-237.


Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci. 2001;24:31-55.

East SJ, Hill MP, Brotchie JM. Metabotropic glutamate receptor agonists inhibit endogenous glutamate release from rat striatal synaptosomes. Eur J Pharmacol. 1995;277:117-121.

Ewing JF, Maines MD. In situ hybridization and immunohistochemical localization of heme oxygenase-2 mRNA and protein in normal rat brain: differential distribution of isozyme1 and 2. Mol Cell neurosci. 1992;3:559-570.

Foley CM, Moffitt JA, Hay M, Hasser EM. Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors. Am J Physiol. 1998;275:R1858-1866.

Fredholm BB, Hedqvist P. Modulation of neurotransmission by purine nucleotides and nucleosides. Biochem Pharmacol. 1980;29:1635-1643.

Fredholm BB, Duner-Engstrom M, Fastbom J, Jonzon B, Lindgren E, Norstedt C, Pedata F, Van den Ploeg I. Interactions between the neuromodulator adenosine and the classic transmitters. Topics and Perspectives in Adenosine Research, ed. by Gerlach E, Becker BF, Springer-Verlag, Berlin, 1987, pp.499-508.


Glaum SR, Miller RJ. Metabotropic glutamate receptors mediate excitatory transmission in the nucleus of the solitary tract. J Neurosci. 1992;12:2251-2258.

Glaum SR, Miller RJ. Activation of metabotropic glutamate receptors produces reciprocal regulation of ionotropic glutamate and GABA responses in the nucleus of the tractus solitarius of the rat. J Neurosci. 1993a;13:1636-1641.

Glaum SR, Miller RJ. Zinc protoporphyrin-IX blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarii. Mol Pharmacol. 1993b;43:965-969.

Glitsch M, Llano I, Marty A. Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum. J Physiol. 1996;497:531-537.

Hay M, McKenzie H, Lindsley K, Dietz N, Bradley SR, Conn PJ, Hasser EM. Heterogeneity of metabotropic glutamate receptors in autonomic cell groups of the medulla oblongata of the rat. J Comp Neurol. 1999;403:486-501.

Herrero I, Miras-Portugal MT, Sanchez-Prieto J. Rapid desensitization of the metabotropic glutamate receptor that facilitates glutamate release in rat cerebrocortical nerve terminals. Eur J Neurosci. 1994;6:115-120.
Hylland P, Nilsson GE, Lutz PL. Time course of anoxia-induced increase in cerebral blood flow rate in turtles: evidence for a role of adenosine. J Cereb Blood Flow Metab. 1994;14:877-881.

Johnson RA, Lavesa M, Askari B, Abraham NG, Nasjletti A. A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats. Hypertension. 1995;25:166-169.

Johnson RA, Lavesa M, DeSeyn K, Scholer MJ, Nasjletti A. Heme oxygenase substrates acutely lower blood pressure in hypertensive rats. Am J Physiol. 1996;271:H1132-1138.

Johnson RA, Colombari E, Colombari DS, Lavesa M, Talman WT, Nasjletti A. Role of endogenous carbon monoxide in central regulation of arterial pressure. Hypertension. 1997;30:962-967.

Johnson RA, Johnson FK. The effects of carbon monoxide as a neurotransmitter. Curr Opin Neurol. 2000;13:709-713.

Jones NM, Lawrence AJ, Beart PM. In vivo microdialysis reveals facilitatory metabotropic glutamate receptors regulating excitatory amino acid release in rat nucleus tractus solitarius. Neurochem Int. 1998;32:31-38.

Ko KR, Ngai AC, Winn HR. Role of adenosine in regulation of regional cerebral blood flow in sensory cortex. Am J Physiol. 1990;259:H1703-1708.
Komuro T, Borsody MK, Ono S, Marton LS, Weir BK, Zhang ZD, Paik E, Macdonald RL. The vasorelaxation of cerebral arteries by carbon monoxide. Exp Biol Med (Maywood). 2001;226:860-5.

Latini S, Pedata F. Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem. 2001;79:463-484.

Linden IB, Tokola O, Karlsson M, Tenhunen R. Fate of haem after parenteral administration of haem arginate to rabbits. J Pharm Pharmacol. 1987 Feb;39:96-102.

Lo WC, Jan CR, Wu SN, Tseng CJ. Cardiovascular effects of nitric oxide and adenosine in the nucleus tractus solitarii of rats. Hypertension. 1998;32:1034-1038.

Lo WC, Jan CR, Chiang HT, Tseng CJ. Modulatory effects of carbon monoxide on baroreflex activation in nucleus tractus solitarii of rats. Hypertension. 2000;35:1253-1257.

Lombardi G, Pellegrini-Giampietro DE, Leonardi P, Cherici G, Pellicciari R, Moroni F. The depolarization-induced outflow of [3H]D-aspartate form rat brain slices is modulated by metabotropic glutamate receptors. Neurochem Int. 1994;24:525-532.


Lombardi G, Leonardi P, Moroni F. Metabotropic glutamate receptors, transmitter output and fatty acids: studies in rat brain slices. Br J Pharmacol. 1996;117:189-195.

Maines MD. Zinc . protoporphyrin is a selective inhibitor of heme oxygenase activity in theneonatal rat. Biochim Biophys Acta. 1981;673:339-350.

Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J. 1988;2:2557-2568.

Maines MD. Carbon monoxide: an emerging regulator of cGMP in the brain. Mol Cell Neurosci. 1993;4:389-397.

Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37:517-554.

Mancuso C, Pistritto G, Tringali G, Grossman AB, Preziosi P, Navarra P. Evidence that carbon monoxide stimulates prostaglandin endoperoxide synthase activity in rat hypothalamic explants and in primary cultures of rat hypothalamic astrocytes. Brain Res Mol Brain Res. 1997;45:294-300.

Marks GS, Brien JF, Nakatsu K, McLaughlin BE. Does carbon monoxide have a physiological function? Trends Pharmacol Sci. 1991;12:185-188.
Matsumura K, Tsuchihashi T, Kagiyama S, Abe I, Fujishima M. Subtypes of metabotropic glutamate receptors in the nucleus of the solitary tract of rats. Brain Res. 1999;842:461-8.

Mosqueda-Garcia R, Tseng CJ, Appalsamy M, Robertson D. Modulatory effects of adenosine on baroreflex activation in the brainstem of normotensive rats. Eur J Pharmacol. 1989;174:119-122.

Mosqueda-Garcia R, Tseng CJ, Appalsamy M, Beck C, Robertson D. Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract. Hypertension. 1991;18:494-502.

Nakanishi S. Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity. Neuron. 1994;13:1031-1037.

Okada D. Two pathways of cyclic GMP production through glutamate receptor-mediated nitric oxide synthesis. J Neurochem. 1992;59:1203-1210.

Pelleg A, Katchanov G, Xu J. Purinergic modulation of neural control of cardiac function. J Auton Pharmacol. 1996;16:401-405.

Phillis JW. Adenosine in the control of the cerebral circulation. Cerebrovasc Brain Metab Rev. 1989;1:26-54.

Reis DJ, Granata AR, Perrone MH, Talman WT. Evidence that glutamic acid is the neurotransmitter of baroreceptor afferent terminating in the nucleus tractus solitarius (NTS). J Auton Nerv Syst. 1981a;3:321-234.

Reis DJ, Perrone H, Talman W. Glutamic acid as the neurotransmitter of baroreceptor afferents in the nucleus tractus solitarii: possible relationship to neurogenic hypertension. In Central Nervous System Mechanisms in Hypertension, ed. by Buckley JP and Ferrario CM, Raven Press, New York, 1981b, pp.37-48.

Rothschuh KE. History of Physiology, Krieger Publishing Company, New York, 1973.

Seller H, Illert M. The localization of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of afferent input. Pfluegers Arch. 1969;306:1-19.

Silva CC, Almeida VA, Haibara AS, Johnson RA, Colombari E. Role of carbon monoxide in L-glutamate-induced cardiovascular responses in nucleus tractus solitarius of conscious rats. Brain Res. 1999;824:147-152.

Takahashi K, Hara E, Suzuki H, Sasano H, Shibahara S. Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors. J Neurochem. 1996;67:482-9.
Talman WT, Perrone MH, Reis DJ. Evidence for L-glutamate as the neurotransmitter of baroreceptor afferent nerve fibers. Science. 1980;209:813-815.

Talman WT. Kynurenic acid microinjected into the nucleus tractus solitarius of rat blocks the arterial baroreflex but not responses to glutamate. Neurosci Lett. 1989;102:247-252.

Toda N, Okamura T. Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arterial tone. Am J Physiol. 1991;261:H1740-1745.

Tseng CJ, Biaggioni I, Appalsamy M, Robertson D. Purinergic receptors in the brainstem mediate hypotension and bradycardia. Hypertension. 1988;11:191-197.

Tseng CJ, Mosqueda-Garcia R, Appalsamy M, Robertson D. Cardiovascular effects of neuropeptide Y in rat brainstem nuclei. Circ Res. 1989;64:55-61.

Tseng CJ, Tung CS. Brainstem and cardiovascular regulation. Disorders of the Autonomic Nervous System, ed. by Robertson D, Biaggioni I, Harwood Academic Publishers, London, 1995, pp.9–23.



Tseng CJ, Liu HY, Lin HC, Ger LP, Tung CS, Yen MH. Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension. 1996;27:36-42.

Tsuchihashi T, Liu Y, Kagiyama S, Matsumura K, Abe I, Fujishima M. Metabotropic glutamate receptor subtypes involved in cardiovascular regulation in the rostral ventrolateral medulla of rats. Brain Res Bull. 2000;52:279-283.

Vollerthun R, Höhler B, Kummer W. Guinea-pig sympathetic postganglionic neurones contain haem oxygenase-2. Neuroreport. 1995;7:173-176.

Wahl M, Schilling L. Regulation of cerebral blood flow--a brief review. Acta Neurochir Suppl (Wien). 1993;59:3-10.

Wang R, Wang Z, Wu L. Carbon monoxide-induced vasorelaxation and the underlying mechanisms. Br J Pharmacol. 1997;121:927-934.

Winn HR, Rubio GR, Berne RM. The role of adenosine in the regulation of cerebral blood flow. J Cereb Blood Flow Metab. 1981;1:239-244.
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