Champion H C, Pierce R L, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Regul Pept. 1998 Nov 30;78(1-3):69-74. doi: 10.1016/s0167-0115(98)00117-7.
The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, responses to nociceptin were investigated in isolated pressurized resistance arteries from the rat mesenteric vascular bed. Nociceptin in bath concentrations of 10(-9)-10(-6) M induced concentration-dependent increases in arterial diameter when the artery was precontracted with U46619; and administration of the structurally related opioid agonists, dynorphin A and met-enkephalin, had no effect on arterial diameter. Vasodilator responses to nociceptin were not altered by the opioid receptor antagonist naloxone or by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine. Responses to nociceptin were not altered by the muscarinic receptor blocking agent atropine or phentolamine, or the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). These data suggest that nociceptin has direct vasodilator activity that is not dependent upon the activation of a traditional opioid receptor, muscarinic or CGRP receptors, an inhibitory effect on the adrenergic nervous system, or the release of nitric oxide in isolated resistance arteries from the rat mesentery.
十七肽孤啡肽，也称为孤啡肽FQ，是一种最近发现的类阿片G蛋白偶联受体ORL1的内源性配体。在本研究中，研究了大鼠肠系膜血管床离体加压阻力动脉对孤啡肽的反应。当动脉用U46619预收缩时，浴液浓度为10(-9)-10(-6)M的孤啡肽可引起动脉直径呈浓度依赖性增加；而给予结构相关的阿片类激动剂强啡肽A和甲硫氨酸脑啡肽，对动脉直径无影响。孤啡肽的血管舒张反应不受阿片受体拮抗剂纳洛酮或一氧化氮合酶抑制剂N(ω)-硝基-L-精氨酸的影响。毒蕈碱受体阻断剂阿托品或酚妥拉明，以及降钙素基因相关肽(CGRP)受体拮抗剂CGRP-(8-37)均不改变对孤啡肽的反应。这些数据表明，孤啡肽具有直接的血管舒张活性，其不依赖于传统阿片受体、毒蕈碱或CGRP受体的激活，对肾上腺素能神经系统无抑制作用，也不依赖于大鼠肠系膜离体阻力动脉中一氧化氮的释放。
