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

✍ Scribed by Olga L. Caramelo; Paulo F. Santos; Arsélio P. Carvalho; Carlos B. Duarte

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 179 KB
• Volume: 58
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19991115)58:4<505::aid-jnr4>3.0.co;2-j

✦ Synopsis

Retinal amacrine cells express metabotropic glutamate receptors (mGluRs), but their physiological role is unknown. We investigated the effect of mGluR on [ 3 H]acetylcholine release ([ 3 H]ACh) from cultured chick amacrine-like neurons. Activation of group III mGluR with the agonist L(؉)-2-amino-4-phosphonobutyric acid (L-AP4) inhibited [ 3 H]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)-3,5dihydroxyphenylglycine (DHPG) and (2S,2ЈR,3ЈR)-2-(2Ј,3Ј-dicarboxycyclopropyl)glycine (DCG-IV), respectively, did not affect significantly [ 3 H]ACh release. The effect of L-AP4 on [ 3 H]ACh release was sensitive to nitrendipine, suggesting that it is, at least in part, due to inhibition of L-type Ca 2؉ channels. Activation of group III mGluR also partly inhibited -conotoxin GVIA-sensitive Ca 2؉ channels, coupled to [ 3 H]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 [ 3 H]ACh release is not due to inhibition of adenylyl cyclase activity. Inhibition of protein kinase A with KT-5720 was without effect on [ 3 H]ACh release evoked by 25 mM KCl, further indicating that the effect of group III mGluR on [ 3 H]ACh release cannot be attributed to the inhibition of the kinase. The effect of L-AP4 on [ 3 H]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 [ 3 H]ACh release may be due to a direct inhibition of L-and N-type Ca 2؉ channels and is modulated by group I and group II mGluR.