Document Detail

Vasodepressor responses to [D-Ala2]-endomorphin 2 (TAPP) are mediated by an L-NAME-sensitive mechanism in the rat.
MedLine Citation:
PMID:  10028937     Owner:  NLM     Status:  MEDLINE    
Endomorphin 1 and 2 are newly discovered endogenous ligands for the mu-opioid receptor. We recently showed that endomorphin 1 and 2 have vasodepressor activity, and in this study, responses to a novel endomorphin analog [D-Ala2]-endomorphin 2 (TAPP) were investigated in the systemic vascular bed of the rat. Intravenous injections of TAPP, endomorphin 1, and endomorphin 2 decreased systemic arterial pressure in a dose-related manner. Decreases in systemic arterial pressure in response to TAPP were similar to vasodepressor responses to endomorphin 1 and 2 and were not altered by passage of time. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1, and endomorphin 2 were attenuated by the opioid receptor antagonist naloxone (2 mg/kg, i.v.) when the vasodepressor response to the ORL1-receptor agonist nociceptin (orphanin FQ) was not altered. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1 and 2, and acetylcholine were attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg, i.v.) when decreases in systemic arterial pressure in response to nociceptin and calcitonin gene-related peptide (CGRP) were not altered. These results indicate that TAPP, endomorphin 1, and endomorphin 2 decrease systemic arterial pressure by a naloxone-sensitive mechanism and suggest that the vasodepressor response to TAPP, endomorphin 1 and 2, but not nociceptin, is mediated by the release of nitric oxide.
H C Champion; P J Kadowitz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  33     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-05-06     Completed Date:  1999-05-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  280-4     Citation Subset:  IM    
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
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MeSH Terms
Amidines / pharmacology*
Blood Pressure / drug effects*
Calcitonin Gene-Related Peptide / drug effects,  pharmacology
Dose-Response Relationship, Drug
NG-Nitroarginine Methyl Ester / pharmacology*
Naloxone / pharmacology*
Narcotic Antagonists / pharmacology
Opioid Peptides / pharmacology*
Rats, Sprague-Dawley
Receptors, Opioid / antagonists & inhibitors
Somatotypes / physiology
Vasodilation / drug effects
Grant Support
Reg. No./Substance:
0/Amidines; 0/Narcotic Antagonists; 0/Opioid Peptides; 0/Receptors, Opioid; 0/nociceptin; 0/tetra-4-amidinophenoxypropane; 465-65-6/Naloxone; 50903-99-6/NG-Nitroarginine Methyl Ester; 83652-28-2/Calcitonin Gene-Related Peptide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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