mGluR-evoked augmentation of receptor-mediated cyclic AMP formation in neonatal and adult rat striatum

1 The effects of selective agonists at group I, II and III metabotropic glutamate receptors (mGluRs) on adenosine A(2) receptor-mediated cyclic AMP formation were compared in cross-chopped slices of adult and neonatal (8 days old) rat striatum, in the presence of 1 u ml(-1) adenosine deaminase. 2 The group II selective agonist, (2S, 1R, 2R, 3R)-2-(2,3-dicarboxycyclopropyl)gl (DCG-IV), elicited a potentiation of 5'-N-ethylcarboxamidoadenosine (NECA)-stimulated cyclic AMP production with similar potencies in adult (EC50 value 122 +/- 35 nM) and neonatal (EC50 value 285 +/- 6 nM) brain. In contrast, the group I selective agonist (S)-dihydroxyphenylglycine ((S)-DHPG) augmented the NECA cyclic AMP response in neonatal striatum (EC50 value 9 +/- 1 mu M), but at a concentration of 100 mu M, (S)-DHPG failed to affect the NECA response in adult striatal slices. 3 The potentiation evoked by (S)-DHPG was specific for group I mGluRs as (2S,3S,4S,)-2-methyl-2(carboxycyclopropyl)glycine (MCCG), a group II antagonist, was ineffective on the (S)-DHPG (100 mu M) response at a concentration (500 mu M) which reversed a similar augmentation elicited by DCG-IV (300 nM). Furthermore, a protein kinase C inhibitor (Ro 31-8220, 10 mu M) markedly reversed the effect of (S)-DHPG without affecting the response to DCG-IV. 4 The mGluR agonist (2S,3S,4S,)-alpha-carboxycyclopropyl)glycin (L-CCG-I), elicited a greater potentiation of NECA-stimulated cyclic AMP production in neonatal striatum in comparison with that observed in adult rat brain. Moreover, EC50 values obtained from adult and neonatal striatum were 2 +/- 1 mu M and 9 +/- 1 mu M, respectively. These differences in potency might reflect co-activation of both group I and group II mGluRs by L-CCG-I in neonatal striatum. 5 Distinct patterns of mGluR expression in various brain areas might account for previous conflicting data on the nature of the mGluR able to evoke such potentiated responses.