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Am J Physiol Endocrinol Metab 273: E214-E219, 1997;
0193-1849/97 $5.00
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AJP - Endocrinology and Metabolism, Vol 273, Issue 1 E214-E219, Copyright © 1997 by American Physiological Society

ARTICLES

Nociceptin, a novel endogenous ligand for the ORL1 receptor, has potent erectile activity in the cat

H. C. Champion, R. Wang, W. J. Hellstrom and P. J. Kadowitz
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.

The heptadecapeptide nociceptin, also known as orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G protein-coupled receptor ORL1. The present study was undertaken to investigate the effects of intracavernosal injections of nociceptin on penile erection in anesthetized cats. Responses to nociception were compared with erectile responses elicited by intracavernosal injection of vasoactive intestinal polypeptide (VIP), adrenomedullin (ADM), the novel nitric oxide donor diethylaminenitric oxide complex sodium (DEA/NO), and the control triple-drug combination (papaverine, phentolamine, and prostaglandin E1). The order of potency was VIP > ADM > nociceptin > DEA/NO. Intracavernosal injections of nociceptin in doses of 0.3-30 nmol elicited dose-related increases in cavernosal pressure and penile length that were comparable to those induced by the triple-drug combination, which is used in the treatment of erectile dysfunction. The response to nociceptin was rapid in onset, and the duration of the peak pressure increase and total response was significantly shorter than the response to the control triple-drug combination but longer in duration than responses to VIP and ADM. Intracavernosal injection of the triple-drug combination resulted in a greater decrease in mean systemic arterial blood pressure than did nociceptin. These data demonstrate that intracavernosal injection of this novel endogenous ligand for the ORL1 receptor induces a potent and relatively long-lasting erectile response in the cat.


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