NOCICEPTIN, A NOVEL ENDOGENOUS LIGAND FOR THE ORL1 RECEPTOR, HAS POTENT ERECTILE ACTIVITY IN THE CAT

The heptadecapeptide nociceptin, also known as orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G protein-coupled re ceptor ORL1. The present study was undertaken to investigate the effec ts of intracavernosal injections of nociceptin on penile erection in a nesthetized cats. Responses to nociceptin were compared with erectile responses elicited by intracavernosal injection of vasoactive intestin al polypeptide (VIP), adrenomedullin (ADM), the novel nitric oxide don or diethylamine-nitric oxide complex sodium (DEA/NO), and the control triple-drug combination (papaverine, phentolamine, and prostaglandin E -1). The order of potency was VIP > ADM > nociceptin > DEA/NO. Intraca vernosal injections of nociceptin in doses of 0.3-30 nmol elicited dos e-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 nocicep tin 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 combinat ion resulted in a greater decrease in mean systemic arterial blood pre ssure than did nociceptin. These data demonstrate that intracavernosal injection of this novel endogenous ligand for the ORL1 receptor induc es a potent and relatively long-lasting erectile response in the cat.