The endogenous mu-opioid agonists, endomorphin 1 and 2, have vasodilator activity in the hindquarters vascular bed of the rat.
Endomorphin 1 and endomorphin 2 are newly-discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intra-arterial injections of endomorphin 1 and 2 were investigated in the hindquarters vascular bed of the rat. Under constant-flow conditions, endomorphin 1 and 2 induced dose-dependent decreases in hindquarters perfusion pressure when injected in doses of 3-100 nmol into the hindquarters perfusion circuit. Vasodilator responses to endomorphin 1 and 2 and met-enkephalin were attenuated by the opioid receptor antagonist naloxone (2 mg/kg i.v.) at a time when vasodilator responses to isoproterenol were not altered. In terms of relative vasodilator activity, endomorphin 1 and 2 were similar to ATP, 100-fold less potent than isoproterenol, and 10,000-fold less potent than acetylcholine. These data demonstrate that endomorphin 1 and 2 have significant naloxone-sensitive vasodilator activity in the hindquarters vascular bed of the rat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Zadina
J E
JE
Kastin
A J
AJ
Kadowitz
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D014665:Vasodilator Agents; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2; D004744:Enkephalin, Methionine; D000255:Adenosine Triphosphate; D007545:Isoproterenol; D000109:Acetylcholine