INTERACTION BETWEEN A(1) ADENOSINE AND CLASS-II METABOTROPIC GLUTAMATE RECEPTORS IN THE REGULATION OF PURINE AND GLUTAMATE RELEASE FROM RATHIPPOCAMPAL SLICES

Electrical stimulation of rat hippocampal slices evoked the release of excitatory amino acids and purines, as reflected by a time-dependent increase in the extracellular levels of glutamate and adenosine, as we ll as by the increased efflux of radioactivity in slices preloaded wit h both [C-14]glutamate and [H-3]adenosine, The evoked release of excit atory amino acids and purines was amplified when slices were exposed t o 8-cyclopentyl-1,3-dipropyl-xanthine (a selective A1 adenosine recept or antagonist), (+)-alpha-methyl-4-carboxyphenylglycine [a mixed antag onist of metabotropic glutamate receptors (mGluRs)], or (2S,3S,4S)-2-m ethyl-2-(carboxycyclopropyl) glycine (a selective antagonist of class II mGluRs), In contrast, 2-chloro-N-6-cyclopentyladenosine (CCPA; a se lective A1 receptor agonist) or (2S,1R,2R,3R) - (2,3-dicarboxycyclopro pyl)glycine (DCG-IV; a selective agonist of class II mGluRs) reduced t he evoked release of excitatory amino acids and purines, CCPA and DCG- IV also reduced the increase in cyclic AMP formation induced-by either forskolin or electrical stimulation in hippocampal slices. The inhibi tory effect of CCPA and DCG-IV on release or cyclic AMP formation was less than additive, We conclude that the evoked release of excitatory amino acids and purines is under an inhibitory control by A1 receptors A1 receptors and class II mGluRs, i.e., mGluR2 or 3, which appear to operate through a common transduction pathway, In addition, although t hese receptors are activated by endogenous adenosine and glutamate, th ey can still respond to pharmacological agonists. This provides a rati onale or the use of A1 or class II mGluR agonists as neuroprotective a gents-in experimental models of excitotoxic neuronal degeneration.