Document Detail

Carbon monoxide and metabotropic glutamate receptors in rat nucleus tractus solitarii: participation in cardiovascular effect.
MedLine Citation:
PMID:  12409003     Owner:  NLM     Status:  MEDLINE    
Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to biliverdin and CO. Recent studies have demonstrated that CO is involved in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii of rats. The purpose of the present study was to investigate the possible interaction of CO and excitatory amino acids in the nucleus tractus solitarii. In anesthetized male Sprague-Dawley rats, unilateral intranucleus tractus solitarii microinjection of hematin, a heme molecule cleaved by heme oxygenase to yield CO, or excitatory amino acids L-glutamate produced depressor and bradycardiac effects. Similar cardiovascular effects were observed with several agonists for ionotropic glutamate receptors such as N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxyl-5-methylisoxazole-4-propanoic acid (AMPA), kainic acid and for metabotropic glutamate (mGlu) receptors, trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid (ACPD). Among these agonists, prior administration of the heme oxygenase inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) (1 nmol), significantly attenuated the cardiovascular effects of hematin, L-glutamate and ACPD. Furthermore, the cardiovascular effects of ACPD were prevented by the selective mGlu receptors antagonist L-2-amino-3-phosphonoprionate (L-AP3). However, pretreatment with ZnDPBG failed to prevent the cardiovascular responses to microinjection of NMDA, AMPA and kainic acid. On the other hand, prior administration of the NMDA receptor antagonist, diazocilpine (MK-801), or (+/-)-2-amino-5-phosphonopentanoic acid (APV) attenuated the depressor and bradycardiac effect of hematin. These results demonstrated that mGlu receptors may couple to the activation of heme oxygenase via the liberation of CO to participate in central cardiovascular regulation. They also suggested that CO and excitatory amino acids may interact in the nucleus tractus solitarii of rats.
Wan-Chen Lo; Julie Y H Chan; Che-Se Tung; Ching-Jiunn Tseng
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  454     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-31     Completed Date:  2003-06-19     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  39-45     Citation Subset:  IM    
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan, ROC.
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MeSH Terms
Blood Pressure / drug effects
Carbon Monoxide / metabolism*
Cardiovascular System / drug effects*
Cycloleucine / analogs & derivatives*,  pharmacology
Deuteroporphyrins / pharmacology
Dizocilpine Maleate / pharmacology
Excitatory Amino Acid Agonists / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Glutamic Acid / pharmacology
Heart Rate / drug effects
Heme Oxygenase (Decyclizing) / antagonists & inhibitors
Hemin / pharmacology
Kainic Acid / pharmacology
N-Methylaspartate / pharmacology
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / drug effects*,  metabolism
Solitary Nucleus / drug effects*,  metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Reg. No./Substance:
0/Deuteroporphyrins; 0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Receptors, Metabotropic Glutamate; 111900-32-4/1-amino-1,3-dicarboxycyclopentane; 119700-81-1/zinc deuteroporphyrin IX 2,4-bis(glycol); 16009-13-5/Hemin; 487-79-6/Kainic Acid; 52-52-8/Cycloleucine; 56-86-0/Glutamic Acid; 630-08-0/Carbon Monoxide; 6384-92-5/N-Methylaspartate; 77086-22-7/Dizocilpine Maleate; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; EC Oxygenase (Decyclizing)

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