title: Vasodilator responses to the endomorphin peptides, but not nociceptin/OFQ, are mediated by nitric oxide release.
abstract: The endomorphin peptides, endogenous ligands for the mu-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have substantial vasodilator activity in the rat. The roles of nitric oxide, vasodilator prostaglandins, and the opening of K+ATP channels in mediating vasodilator responses to these novel agonists were investigated in the hindquarters vascular bed of the rat. Under constant-flow conditions, injections of the mu-selective agonists, endomorphin 1 and 2, PL017 ([N-MePhe3, D-Pro4]-morphiceptin), and DAMGO, and the ORL1 receptor agonist, nociceptin/OFQ, produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1, PL017, and DAMGO were attenuated by the nitric oxide synthase inhibitor L-NAME at a time when vasodilator responses to nociceptin/OFQ were not altered. Responses to endomorphin 1 and 2, PL017, DAMGO, and nociceptin/OFQ were not altered by the cyclooxygenase inhibitor sodium meclofenamate or the K+ATP channel blocker U-37883A. The results of these studies indicate that responses to endomorphin 1 and 2, PL017, and DAMGO are mediated in large part by the release of nitric oxide, while responses to nociceptin/OFQ are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that responses to these peptides are not mediated by the release of vasodilator prostaglandins or K+ATP channel opening in the hindquarters vascular bed.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. hchampi@welch.jhu.edu
authors.forename: H C
authors.initials: HC
authors.lastname: Champion
authors.forename: T J
authors.initials: TJ
authors.lastname: Bivalacqua
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: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004232:Diuretics / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D000218:Adamantane; D000701:Analgesics, Opioid; D004232:Diuretics; D004723:Endorphins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D008469:Meclofenamic Acid; D009025:Morpholines; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009842:Oligopeptides; D018847:Opioid Peptides; D014665:Vasodilator Agents; D000097629:Nociceptin; C105293:endomorphin 1; C105294:endomorphin 2; C082658:U 37883A; C044708:morphiceptin, N-Me-Phe(3)-