Nitric oxide enhancement of cholinergic amacrine activity by inhibition of glycine release.
OBJECTIVE
To investigate a possible interaction between cholinergic and nitrergic amacrine cells in the rabbit retina.


METHODS
The activity of cholinergic amacrine cells was estimated by measuring the light-evoked release of [3H]-acetylcholine (ACh) from the retina of rabbits anesthetized with urethane. An eyecup was prepared and filled with Krebs-Ringer bicarbonate solution, containing [3H]-choline. After washing with fresh medium containing physostigmine, 0.5 ml of medium was placed in the eyecup. The medium was replaced every 5 minutes, and the radioactivity in the resultant samples was measured. In some experiments the release of [3H]-ACh and glycine was measured using isolated retinas.


RESULTS
Local application of the nitric oxide (NO) donors, S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside strikingly enhanced the light-evoked release of [3H]-ACh. In contrast, inhibition of nitric oxide synthase with L-nitromonomethylarginine (LNMMA) or N-nitro-L-arginine (LNA) greatly reduced the light-evoked release of [3H]-ACh. In that the response of cholinergic amacrine cells is damped by an inhibitory feedback circuit involving glycinergic amacrine cells, the effect of strychnine on the inhibitory action of LNMMA was examined, Strychnine abolished the inhibitory effect of LNMMA on the light-evoked release of [3H]-ACh, suggesting that endogenous NO normally has an inhibitory effect on glycinergic amacrine cells. This idea was supported by experiments using isolated retinas, in which sodium nitroprusside and S-nitroso-N-acetyl-DL-penicillamine inhibited the potassium-evoked release of glycine but enhanced the release of [3H]-ACh.


CONCLUSIONS
Endogenous NO is released in the retina and acts indirectly to facilitate the light-evoked response of cholinergic amacrine cells.
Neal
M
M
Division of Pharmacology, United Medical School of Guy's Hospital, London, United Kingdom.
Cunningham
J
J
Matthews
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004596:Electroretinography; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D011188:Potassium; D005998:Glycine