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 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.
Neal
M J
MJ
Department of Pharmacology, UMDS, St Thomas' Hospital, London.
Cunningham
J R
JR
Paterson
S J
SJ
McKnight
A T
AT
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D008027:Light; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018847:Opioid Peptides / Q000494:pharmacology*; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D000097629:Nociceptin
D000109:Acetylcholine; D009270:Naloxone; D018847:Opioid Peptides; D011950:Receptors, Cholinergic; D017450:Receptors, Opioid, mu; D000097629:Nociceptin