title: Endomorphin 1 and 2, the endogenous mu-opioid agonists, produce biphasic changes in systemic arterial pressure in the cat.
abstract: The endogenous peptides endomorphin 1 and 2 are newly isolated, potent, selective mu-opioid receptor agonists. In the present study, responses to the endomorphin peptides were investigated in the systemic vascular bed of the cat. Endomorphin 1 and 2 induced dose-related biphasic changes in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. The biphasic responses to endomorphin 1 and 2 were characterized by an initial increase followed by a decrease in systemic arterial pressure. In terms of relative vasodepressor activity, endomorphin 1 and 2 were similar in potency and approximately 10-fold less potent than the ORL1 ligand nociceptin (orphanin FQ) in decreasing systemic arterial pressure. The biphasic arterial pressure changes in response to endomorphin 1 and 2 were inhibited by the opioid receptor antagonist naloxone in a dose of 2 mg/kg i.v. These results demonstrate that endomorphin 1 and 2 produce significant, naloxone-sensitive changes in systemic arterial pressure that are characterized by an initial increase followed by a secondary decrease in arterial pressure in the cat.
authors.affiliation: Department of Pharmacology, Tulane Medical School, New Orleans, Louisiana 70112, USA. champion@mailhost.tcs.tulane.edu
authors.forename: H C
authors.initials: HC
authors.lastname: Champion
authors.forename: T J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: D G
authors.initials: DG
authors.lastname: Lambert
authors.forename: S M
authors.initials: SM
authors.lastname: McWilliams
authors.forename: J E
authors.initials: JE
authors.lastname: Zadina
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2