Evidence for a cholinergic inhibitory feed-back mechanism in the rabbit retina.

The effects of muscarine, atropine and nicotinic antagonists on the light-evoked release of radioactivity from rabbit retinas previously exposed to [3H]choline (Ch) was studied. On the basis of previous experiments, this light-evoked release of total radioactivity was taken as a measure of the light-evoked release of [3H]acetylcholine (ACh) from the cholinergic amacrine cells. Atropine (1 microM) in the presence, but not the absence, of eserine more than doubled the light-evoked release of [3H]ACh. Eserine (30 microM) itself had no significant effect on either the spontaneous resting release or the light-evoked release of [3H]ACh. Muscarine (10 microM) in the presence or absence of eserine reduced the light-evoked release of [3H]ACh from the retina by 50%. This effect of muscarine was blocked by atropine used in the absence of eserine. The nicotinic antagonists pempidine, hexamethonium and gallamine had no significant effect on retinal [3H]ACh release. Strychnine (20 microM), which alone had no effect on retinal [3H]ACh release, abolished the effects of both muscarine and atropine on the light-evoked release of [3H]ACh. Bicuculline (5 microM) did not affect the actions of muscarine or atropine on the light-evoked release of [3H]ACh. Previous experiments had shown that glycine and gamma-aminobutyric acid (GABA) reduce the light-evoked release of [3H]ACh from the retina and that these inhibitory effects are selectively blocked by strychnine (20 microM) and bicuculline (5 microM) respectively. These results suggest the presence in the retina of a cholinergic inhibitory feed-back mechanism which involves a neuronal loop, rather than presynaptic or post-synaptic inhibitory muscarinic receptors on the cholinergic amacrine cells themselves. Our experiments do not provide evidence on the nature of the proposed inhibitory loop, except that it apparently includes a glycinergic or taurinergic (amacrine) cell.