Metabotropic glutamate receptors modulate [H-3]acetylcholine release from cultured amacrine-like neurons

Retinal amacrine cells express metabotropic glutamate receptors (mGluRs), b ut their physiological role is unknown. We investigated the effect of mGluR an [H-3]acetylcholine release ([H-3]ACh) from cultured chick amacrine-like neurons, Activation of group III mGluR with the agonist L(+)-2-amino-4-pho sphonobutyric acid (L-AP4) inhibited [H-3]ACh release evoked by 25 mM KCl i n a dose-dependent manner, and this effect was sensitive to pertussis toxin . In contrast, activation of group I or II mGluR with (S)-3,5-dihydroxyphen ylglycine (DHPG) and (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DC G-IV), respectively, did not affect significantly [H-3]ACh release. The eff ect of L-AP4 on [H-3]ACh release was sensitive to nitrendipine, suggesting that it is, at least in part, due to inhibition of L-type Ca2+ channels, Ac tivation of group III mGluR also partly inhibited omega-conotoxin GVIA-sens itive Ca2+ channels, coupled to [H-3]ACh release. The L-AP4 did not affect the cAMP levels measured in amacrine-like neurons depolarized with 25 mM KC l or stimulated with forskolin, indicating that the effect of group III mGl uR on [H-3]ACh release is not due to inhibition of adenylyl cyclase activit y, Inhibition of protein kinase A with KT-5720 was without effect on [H-3]A Ch release evoked by 25 mM KCl, further indicating that the effect of group III mGluR on [H-3]ACh release cannot be attributed to the inhibition of th e kinase, The effect of L-AP4 on [H-3]ACh release was reversed by DHPG or b y DCG-IV, and activation of group II mGluR also partially inhibited cAMP pr oduction stimulated by forskolin, Taken together, our results show that the effect of group III mGluR on [H-3]ACh release may be due to, a direct inhi bition of L- and N-type Ca2+ channels and is modulated by group I and group II mGluR, J. Neurosci. Res. 58:505-514, 1999. (C) 1999 Wiley-Liss, Inc.