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Vasodilator Responses to the Endomorphin Peptides, but Not Nociceptin/OFQ, Are Mediated by Nitric Oxide Release
Author(s) -
CHAMPION H. C.,
BIVALACQUA T. J.,
ZADINA J. E.,
KASTIN A. J.,
KADOWITZ P. J.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07888.x
Subject(s) - nociceptin receptor , nitric oxide , chemistry , pharmacology , vasodilation , medicine , opioid peptide , receptor , biochemistry , opioid , organic chemistry
A bstract : The endomorphin peptides, endogenous ligands for the μ‐opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL 1 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 ‐MePhe 3 , d‐Pro 4 ]‐morphiceptin), and DAMGO, and the ORL 1 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.