Champion H C, Bivalacqua T J, Wang R, Hellstrom W J, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Androl. 1998 Nov-Dec;19(6):747-53.
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.
十七肽孤啡肽，也称为孤啡肽FQ，是一种新发现的类阿片G蛋白偶联受体ORL1的内源性配体。本研究旨在探究阴茎海绵体内注射孤啡肽类似物[酪氨酸1] - 孤啡肽的反应，并研究纳洛酮对麻醉猫对[酪氨酸1] - 孤啡肽和孤啡肽勃起反应的影响。阴茎海绵体内注射0.3 - 30 nmol剂量的[酪氨酸1] - 孤啡肽和孤啡肽可引起海绵体压力与剂量相关的增加，在所研究的最高剂量下，其增加程度与三联药物标准制剂（罂粟碱、酚妥拉明和前列腺素E1）诱导的增加程度相当，该制剂用于治疗勃起功能障碍。对[酪氨酸1] - 孤啡肽的反应起效迅速，其时间进程与对孤啡肽的反应相似。甲硫脑啡肽可增加海绵体压力，而注射孤啡肽 - （2 - 17）、强啡肽A和β - 内啡肽则不会改变海绵体压力。在对甲硫脑啡肽的勃起反应减弱时，给予阿片受体拮抗剂纳洛酮后，对孤啡肽和[酪氨酸1] - 孤啡肽的勃起反应未发生改变。这些数据表明，[酪氨酸1] - 孤啡肽和孤啡肽在猫中具有相似的对纳洛酮不敏感的勃起活性。
