[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 E1), 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 beta-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.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Bivalacqua
T J
TJ
Wang
R
R
Hellstrom
W J
WJ
Kadowitz
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000819:agonists; D000097629:Nociceptin
D009270:Naloxone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C106528:nociceptin, Tyr(1)-