title: Metabotropic glutamate receptors modulate [(3)H]acetylcholine release from cultured amacrine-like neurons.
abstract: 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, 5-dihydroxyphenylglycine (DHPG) and (2S,2'R,3'R)-2-(2', 3'-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 omega-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.
authors.affiliation: Center for Neuroscience of Coimbra, Department of Zoology, University of Coimbra, Coimbra, Portugal.
authors.forename: O L
authors.initials: OL
authors.lastname: Caramelo
authors.forename: P F
authors.initials: PF
authors.lastname: Santos
authors.forename: A P
authors.initials: AP
authors.lastname: Carvalho
authors.forename: C B
authors.initials: CB
authors.lastname: Duarte
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002794:Choline / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D018094:Receptors, Metabotropic Glutamate; D005576:Colforsin; D015761:4-Aminopyridine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002794:Choline; D000109:Acetylcholine