Endomorphin 1 and 2, endogenous mu-opioid agonists, decrease systemic arterial pressure in the rat.
The endogenous opioid peptides, endomorphin 1 and 2, are newly isolated, potent, and selective mu-opioid receptor agonists. In the present study, responses to endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 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, endomorphin 1 and 2 were approximately equipotent with each other and with the ORL1 ligand, nociceptin (orphanin FQ), and were about 10-fold more potent than met-enkephalin in decreasing systemic arterial pressure. Vasodepressor responses to endomorphin 1 and 2 and met-enkephalin, but not to nociceptin, were inhibited by the opioid receptor antagonist, naloxone. These results demonstrate that endomorphin 1 and 2 produce significant naloxone-sensitive decreases in systemic arterial pressure.
Czapla
M A
MA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Champion
H C
HC
Zadina
J E
JE
Kastin
A J
AJ
Hackler
L
L
Ge
L J
LJ
Kadowitz
P J
PJ
D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014662:Vasoconstrictor Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D004744:Enkephalin, Methionine; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D014662:Vasoconstrictor Agents; D000097629:Nociceptin; C105293:endomorphin 1; C105294:endomorphin 2