Inhibition by nociceptin of the light-evoked release of ACh from retinal cholinergic neurones

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 mu M) 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 [H-3]-nociceptin indicating the presence of ORLI-receptors. Since [des-Phe(1)]-nociceptin, which has no affinity for the ORLI-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 ORLI receptors.