Baclofen enhancement of acetylcholine release from amacrine cells in the rabbit retina by reduction of glycinergic inhibition.
1. The mechanism by which the GABAB-receptor agonist, baclofen, enhances the light-evoked release of [3H]acetylcholine (ACh) from cholinergic amacrine cells was studied using an eye-cup preparation in anaesthetized rabbits and isolated retinas. 2. When applied locally to the rabbit retina, baclofen increased the release of ACh evoked by a flickering light (3 Hz) by over 40%. 3. In isolated retinas, baclofen strikingly inhibited the K(+)-evoked release of glycine but had no effect on GABA release. 4. In the rabbit eye cup, strychnine enhanced the light-evoked release of ACh to a similar degree to that produced by baclofen. The effects of baclofen and strychnine on the light-evoked release of ACh were not additive. In contrast, bicuculline did not affect the enhancing action of baclofen on the light-evoked release of ACh. 5. In order to see whether the glycinergic amacrine cells might be stimulated by ACh, isolated rat and rabbit retinas were exposed to muscarine. This cholinergic agonist potentiated the K(+)-evoked release of glycine by 54%. 6. We suggest that baclofen enhances the light-evoked release of ACh from amacrine cells by inhibiting glycine release from glycinergic amacrine cells which are stimulated by ACh and form an inhibitory feedback loop to the cholinergic neurones.
Neal
M J
MJ
Department of Pharmacology, United Medical and Dental School, St Thomas's Hospital, London, UK.
Cunningham
J R
JR
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; C068457:3-aminopropyl(methyl)phosphinic acid; D005680:gamma-Aminobutyric Acid; D009116:Muscarine; D001418:Baclofen; D013331:Strychnine; D000109:Acetylcholine; D005998:Glycine; D001640:Bicuculline