Vasodilator responses to the endomorphin peptides, but not nociceptin/OFQ, are mediated by nitric oxide release

H. C. Champion, T. J. Bivalacqua, J. E. Zadina, A. J. Kastin, Philip J. Kadowitz

Research output: Contribution to journalArticle

Abstract

The endomorphin peptides, endogenous ligands for the μ-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 μ-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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume897
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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