Potentiation of dopamine-induced cAMP formation by group I metabotropic glutamate receptors via protein kinase C in cultured striatal neurons

Abstract

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.

Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

“…Moreover, both D1R and NMDA receptors in the accumbens appear critical for the early consolidation of appetitive Pavlovian memories (Dalley et al, 2005). These reports are particularly relevant in the context of our current findings, given the close interactions between mGluR5 and D1R (Paolillo et al, 1998;Voulalas et al, 2005;Schotanus and Chergui, 2008) and NMDA receptors (Pisani et al, 2001;Mao and Wang, 2002;Choe et al, 2006) in the striatum. Thus, it is possible that impaired incentive learning and relapse-like behaviors in mGluR5 KD-D1 mice were due, in part, to changes in striatal D1R and NMDA receptor function as a consequence of mGluR5 loss.…”

“…Although mGluR5 is densely expressed on both D1-and D2-MSN populations (Tallaksen-Greene et al, 1998), converging lines of research would suggest that mGluR5 located specifically on D1-MSNs is ideally positioned to influence associative reward-learning processes that may underpin relapse triggered by drug-paired stimuli. First, there is evidence that striatal dopamine D1 receptors (D1R) play a critical role in both the consolidation of associative reward-learning memories (Dalley et al, 2005) and many of the long-term effects of addictive drugs (Anderson and Pierce, 2005) and second, mGluR5 appears to interact closely with D1Rs to regulate striatal neurotransmission (Paolillo et al, 1998;Voulalas et al, 2005;Schotanus and Chergui, 2008).…”

cAMP-dependent Protein Kinase Induces cAMP-response Element-binding Protein Phosphorylation via an Intracellular Calcium Release/ERK-dependent Pathway in Striatal Neurons

“…This model is in contrast with what was found by other authors in PC12 cells (16), in which depolarization-induced Ca 2ϩ entry activates the ERK pathway via a two-step mechanism involving first PKA and then Rap1. In a previous study (33) and in experiments not reported here, we found that, in cultured striatal neurons, Ca 2ϩ entry induced by a Ca 2ϩ ionophore or by depolarization inhibits cAMP formation, probably interacting with the Ca 2ϩ -inhibitable type V adenylyl cyclase isoform, which is abundantly expressed in these neurons (18).…”

“…Trizol, fetal bovine serum, horse serum, and all reagents for cell cultures were from Life Technologies, Inc. The protein kinases inhibitors N- [2-(p- Cell Culture-Primary cultures were obtained as previously described (18). Briefly, striata of 16 -17-day-old Harlan Sprague-Dawley rat embryos were dissected and incubated with papain.…”

Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons

“…Although molecular details are lacking, a number of published reports provide evidence suggesting that significant interactions occur between pathways activated by mGluR and dopamine receptors in the striatum (Berke et al, 1998;Paolillo et al, 1998;Calabresi et al, 1999;Hanania and Johnson, 1999). In primary cultures derived from E18 striatum, we found that stimulation of neurons with 10 M DHPG together with 10 M R(ϩ)SKF38393 enhanced ERK2 phosphorylation (see Fig.…”