Neal M J, Cunningham J R, Paterson S J, McKnight A T
Department of Pharmacology, UMDS, St Thomas' Hospital, London.
Br J Pharmacol. 1997 Apr;120(8):1399-400. doi: 10.1038/sj.bjp.0701135.
The retina possesses cholinergic amacrine cells which release acetylcholine (ACh) in response to flickering light. Using an eye-cup preparation in anaesthetized rabbits we found that when the retina was exposed to nociceptin, the light-evoked release of ACh was reduced in a concentration-dependent manner (IC50 = 100 nM), the maximum effect being 60% inhibition. Opioid receptors were not involved in the inhibitory effect of nociceptin because its action was not blocked by naloxone (1 microM) and furthermore mu-opioids enhanced the light-evoked release of ACh. Using rabbit retina homogenates we found that the retina possessed a substantial number of high-affinity binding sites for [3H]-nociceptin indicating the presence of ORL1-receptors. Since [des-Phe1]-nociceptin, which has no affinity for the ORL1-receptor, had no effect on the light-evoked release of ACh it is unlikely that the action of nociceptin was simply non-specific. We conclude that the inhibitory effect of nociceptin on retinal ACh release involves activation of the ORL1 receptors.
视网膜含有胆碱能无长突细胞，这些细胞会在受到闪烁光刺激时释放乙酰胆碱（ACh）。在麻醉兔的眼杯制备实验中，我们发现当视网膜暴露于孤啡肽时，光诱发的ACh释放以浓度依赖的方式减少（IC50 = 100 nM），最大效应为60%抑制。阿片受体不参与孤啡肽的抑制作用，因为其作用不受纳洛酮（1 μM）的阻断，此外μ-阿片类药物还增强了光诱发的ACh释放。使用兔视网膜匀浆，我们发现视网膜具有大量与[3H]-孤啡肽的高亲和力结合位点，表明存在ORL1受体。由于对ORL1受体没有亲和力的[去苯丙氨酸1]-孤啡肽对光诱发的ACh释放没有影响，因此孤啡肽的作用不太可能仅仅是非特异性的。我们得出结论，孤啡肽对视网膜ACh释放的抑制作用涉及ORL1受体的激活。
