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

• Published in: Journal of neuroscience research 1999-11, Vol.58 (4), p.505-514
• Main Authors: Caramelo, Olga L., Santos, Paulo F., Carvalho, Arsélio P., Duarte, Carlos B.
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Acetylcholine - metabolism; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - metabolism; Animals; Calcium Channel Blockers - pharmacology; calcium channels; Calcium Channels, L-Type - metabolism; Calcium Channels, N-Type - metabolism; cAMP; Cells, Cultured; Chick Embryo; Choline - metabolism; Colforsin - pharmacology; Cyclic AMP - metabolism; G proteins; L-AP4; Neurons - metabolism; Receptor Cross-Talk - drug effects; Receptor Cross-Talk - physiology; Receptors, Metabotropic Glutamate - physiology; retina; Retina - cytology; Retina - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(19991115)58:4<505::AID-JNR4>3.0.CO;2-J

Retinal amacrine cells express metabotropic glutamate receptors (mGluRs), but their physiological role is unknown. We investigated the effect of mGluR on [3H]acetylcholine release ([3H]ACh) from cultured chick amacrine‐like neurons. Activation of group III mGluR with the agonist L(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4) inhibited [3H]ACh release evoked by 25 mM KCl in 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‐dihydroxyphenylglycine (DHPG) and (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), respectively, did not affect significantly [3H]ACh release. The effect of L‐AP4 on [3H]ACh release was sensitive to nitrendipine, suggesting that it is, at least in part, due to inhibition of L‐type Ca2+ channels. Activation of group III mGluR also partly inhibited ω‐conotoxin GVIA‐sensitive Ca2+ channels, coupled to [3H]ACh release. The L‐AP4 did not affect the cAMP levels measured in amacrine‐like neurons depolarized with 25 mM KCl or stimulated with forskolin, indicating that the effect of group III mGluR on [3H]ACh release is not due to inhibition of adenylyl cyclase activity. Inhibition of protein kinase A with KT‐5720 was without effect on [3H]ACh release evoked by 25 mM KCl, further indicating that the effect of group III mGluR on [3H]ACh release cannot be attributed to the inhibition of the kinase. The effect of L‐AP4 on [3H]ACh release was reversed by DHPG or by DCG‐IV, and activation of group II mGluR also partially inhibited cAMP production stimulated by forskolin. Taken together, our results show that the effect of group III mGluR on [3H]ACh release may be due to a direct inhibition of L‐ and N‐type Ca2+ channels and is modulated by group I and group II mGluR. J. Neurosci. Res. 58:505–514, 1999. © 1999 Wiley‐Liss, Inc.