EFFECT OF METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION ON RECEPTOR-MEDIATED CYCLIC-AMP RESPONSES IN PRIMARY CULTURES OF RAT STRIATAL NEURONS

Co-activation of group I metabotropic glutamate (mGlu) receptors and a denosine receptors resulted in an augmented cyclic AMP response in pri mary cultures of rat striatal neurones. L-glutamate and the selective group I agonist, (S)-dihydroxyphenylglycine (S-DHPG) evoked concentrat ion-dependent potentiations of cyclic AMP accumulation stimulated by t he adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), with EC50 values of 3.41 +/- 0.39 and 5.69 +/- 1.64 mu M, respectively , and maximal augmentations of approximately 350% at concentrations of 100 mu M. The S-DHPG potentiation was inhibited by group I mGlu recep tor antagonists and a protein kinase C inhibitor, Po 31-8220, implicat ing products of PI hydrolysis in this effect. Furthermore, L-glutamate and S-DHPG stimulated PI hydrolysis in striatal neuronal cultures wit h similar EC50 values to those observed for the augmentation of NECA c yclic AMP responses (5.19 +/- 1.18 and 3.78 +/- 1.42 mu M, respectivel y). In situ hybridization and immunofluorescence techniques indicate t hat group I mGlu receptor-evoked potentiations are likely to be mediat ed via mGlu(5) receptors, which are expressed at high levels in these cultures. In contrast to cross-chopped slices of neonatal rat striatum , of equivalent age, the group II mGlu receptor agonist, (2S,2'R,3'R)- 2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) was without effect on N ECA- or forskolin-stimulated cyclic AMP responses in primary striatal neuronal cultures. This lack of effect might be due to a low level of expression of group II mGlu receptors in cultured striatal neurones. ( C) 1998 Elsevier Science B.V.