[Tyr¹]-nociceptin and nociceptin have similar naloxone-insensitive 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 receptor ORL₁. The present study was undertaken to investigate responses to intracavernosal injections of the nociceptin analog [Tyr¹]-nociceptin and to investigate the effects of naloxone on erectile responses in anesthetized cats to [Tyr¹]-nociceptin and to nociceptin. Intracavernosal injections of [Tyr¹]-nociceptin and of nociceptin in doses of 0.3-30 nmol elicited dose- related increases in cavernosal pressure, which, at the highest dose studied, were comparable to increases induced by the triple-drug standard (papaverine, phentolamine, and prostaglandin E,), a preparation used in the treatment of erectile dysfunction. Responses to [Tyr¹]-nociceptin were rapid in onset and had a time course similar to responses to nociceptin. Metenkephalin increased cavernosal pressure, whereas injections of nociceptin-(2-17), dynorphin A, and β-endorphin did not alter cavernosal pressure. Erectile responses to nociceptin and to [Tyr¹]-nociceptin were not altered after administration of the opioid receptor antagonist naloxone at a time when erectile responses to metenkephalin were attenuated: These data show that [Tyr¹]-nociceptin and nociceptin have similar naloxone-insensitive erectile activity in the cat.