POTENTIATION OF DOPAMINE-INDUCED CAMP FORMATION BY GROUP-I METABOTROPIC GLUTAMATE RECEPTORS VIA PROTEIN-KINASE-C IN CULTURED STRIATAL NEURONS

Metabotropic glutamate receptors have been shown to potentiate the cyc lic adenosine monophosphate (cAMP) formation induced by activation of several receptors linked to adenylyl cyclase via Os-protein, Here we s how that, in primary cultures of striatal neurons, group I metabotropi c receptors potentiate the cAMP formation induced by activation of D-1 -like dopamine receptors. Reverse transcription associated with polyme rase chain reaction revealed that mGluR5, mGluR3, mGluR4 and mGluR7 ar e present in striatal cell cultures, The potentiation of cAMP formatio n is induced by the selective group I mGluRs agonist (S)-3,5-dihydroxy phenylglycine and by other non-selective mGluRs agonists with a typica l group I-like pharmacology (quisqualate > ibotenate > 1-aminocyclopen tane-1,3-dicarboxylic acid). The rank order potency of mGluRs agonists in potentiating cAMP formation correlates with their ability to induc e inositol phosphates production; the potentiation of cAMP formation a nd the inositol phosphates production are blocked by the group I mGluR s antagonists (S)-4-carboxyphenylglycine and are not affected by group II antagonist 2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine or gr oup III antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid. The potentiating mechanism involves the activation of protein kinase C, be ing mimicked by phorbol-12-myristate-13-acetate and blocked by the spe cific protein kinase C inhibitors bisindolylmaleimide I and chelerythr ine or by protein kinase C downregulation, Our results indicate that t his interaction could have a functional importance in modulating the c AMP-dependent transmission in the striatum.