The endogenous mu-opioid receptor agonists endomorphins 1 and 2 have novel hypotensive activity in the rabbit.
The endogenous peptides endomorphins 1 and 2 are newly isolated, potent, and selective mu-opioid receptor agonists. In the present study, responses to the endomorphin peptides were investigated in the systemic vascular bed of the rabbit. Endomorphins 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, endomorphins 1 and 2 were similar to the ORL1 receptor ligand, nociceptin (Orphanin FQ), and met-enkephalin in decreasing systemic arterial pressure. Vasodepressor responses to endomorphins 1 and 2 were inhibited by the opioid receptor antagonist, naloxone, in a dose of 2 mg/kg i.v. These results demonstrate that endomorphins 1 and 2 have significant naloxone-sensitive, vasodepressor activity in the rabbit.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. champion@mailhost.tcs.tulane.edu
Zadina
J E
JE
Kastin
A J
AJ
Hackler
L
L
Ge
L J
LJ
Kadowitz
P J
PJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D011817:Rabbits; D017450:Receptors, Opioid, mu / Q000819:agonists*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D000959:Antihypertensive Agents; D004744:Enkephalin, Methionine; D009270:Naloxone; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D000097629:Nociceptin; C105293:endomorphin 1; C105294:endomorphin 2