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 cyclic adenosine monophosphate (cAMP) formation induced by activation of several receptors linked to adenylyl cyclase via Gs-protein. Here we show that, in primary cultures of striatal neurons, group I metabotropic receptors potentiate the cAMP formation induced by activation of D1-like dopamine receptors. Reverse transcription associated with polymerase chain reaction revealed that mGluR5, mGluR3, mGluR4 and mGluR7 are present in striatal cell cultures. The potentiation of cAMP formation is induced by the selective group I mGluRs agonist (S)-3,5-dihydroxyphenylglycine and by other non-selective mGluRs agonists with a typical group I-like pharmacology (quisqualate > ibotenate > 1-aminocyclopentane-1,3-dicarboxylic acid). The rank order potency of mGluRs agonists in potentiating cAMP formation correlates with their ability to induce inositol phosphates production; the potentiation of cAMP formation and the inositol phosphates production are blocked by the group I mGluRs antagonists (S)-4-carboxyphenylglycine and are not affected by group II antagonist 2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine or group III antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid. The potentiating mechanism involves the activation of protein kinase C, being mimicked by phorbol-12-myristate-13acetate and blocked by the specific protein kinase C inhibitors bisindolylmaleimide I and chelerythrine or by protein kinase C downregulation. Our results indicate that this interaction could have a functional importance in modulating the cAMP-dependent transmission in the striatum.
Paolillo
M
M
Istituto di Farmacologia, Facoltà di Farmacia, Università di Pavia, Italy.
Montecucco
A
A
Zanassi
P
P
Schinelli
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004298:Dopamine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium; D004298:Dopamine