Role of metabotropic glutamate receptors in the depression of GABA-mediated depolarization of frog primary afferent terminals

摘要: Sucrose gap recordings from the dorsal roots of isolated, hemisected frog spinal cords were used to determine effects metabotropic L-glutamate receptor activation on primary afferent terminals by (+/-)-1-amino-trans-1,3-cyclopentane-dicarboxylic acid (t-ACPD). Dorsal root potentials evoked ventral volleys significantly reduced t-ACPD (30 microM), as GABA- and muscimol-induced terminal depolarizations. The GABA-depolarizations depended upon group I glutamate receptors, i.e. blocked I/II antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, but not II alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine or III alpha-methyl-(S)-2-amino-4-phosphonobutyrate mimicked agonist 3,5-dihydroxyphenylglycine (S)-2-amino-4-phosphonobutyrate. Increasing intracellular concentration 3'-5'-cyclic adenosine monophosphate with 8-bromo-cAMP, forskolin, 3-isobutyl-1-methylxanthine GABA depolarizations, protein kinase inhibitors Rp-adenosine 3,5-cyclic monophosphothioate triethylamine N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide did alter t-ACPD's depression actions depolarizations neither nor phorbol-12-myristate 13-acetate, thapsigargin, staurosporine, arachidonic acid, presumptive indications that involve phosphoinositide hydrolysis, release Ca2+ stores, formation arachidonate. 20 mM Mg2+, broad spectrum kynurenate, selective N-methyl-D-aspartate D(-)-2-amino-5-phosphonovaleric non-N-methyl-D-aspartate 6-cyano-7-nitroquinoxaline-2,3-dione. Low concentrations (10 microM) effect responses. These results suggest involves an indirect, three-stage mechanism includes Group receptors interneurons and/or terminals, latter structures, terminals. caused leads a block presynaptic inhibition (produced in cord GABA) resulting positive feed-forward amplification reflex transmission.