Endomorphin 1 and 2 have vasodepressor activity in the anesthetized mouse.
The endogenous peptides endomorphin 1 and 2 are newly discovered, potent, selective mu-opioid receptor agonists. In the present study, we investigated responses to the endomorphin peptides in the systemic vascular bed of the anesthetized mouse. Endomorphin 1 and 2 induced dose-related decreases in mean arterial pressure when injected in doses of 3-100 nmol/kg i.v. Mean arterial pressure decreased 14 +/- 4, 23 +/- 4, and 42 +/- 5 mm Hg at the 10, 30, and 100 nmol/kg doses, respectively, of endomorphin 1 (n = 5-7; p < 0.05), and similar changes were observed in response to endomorphin 2. In terms of relative vasodepressor activity, endomorphin 1 and 2 were about equipotent and about threefold more potent than the mu-opioid selective agonist PL017 in decreasing mean arterial pressure; all three peptides decreased heart rate. The time-course of the vasodepressor responses to endomorphin 1 and 2 were similar in rate of onset and decay. Vasodepressor responses to endomorphin 1 and 2 and PL017 but not to nociceptin were inhibited by the opioid receptor antagonist naloxone in a dose of 2 mg/kg i.v. When compared in the mouse and rat, the relative decreases in systemic arterial pressure in response to i.v. injections of endomorphin 1 and 2 did not differ greatly. However, the duration of the vasodepressor response was significantly longer in the rat. These results demonstrate that endomorphin 1 and 2 have significant, naloxone-sensitive, vasodepressor activity in the mouse.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Zadina
J E
JE
Kastin
A J
AJ
Kadowitz
P J
PJ
D000704:Analysis of Variance; D000777:Anesthetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000777:Anesthetics; D004723:Endorphins; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D014665:Vasodilator Agents; C105293:endomorphin 1; C105294:endomorphin 2; C044708:morphiceptin, N-Me-Phe(3)-