Functional evidence for presynaptic P2X7 receptors in adult rat cerebrocortical nerve terminals

The presynaptic P2X(7) receptor (P2X(7)R) plays an important role in the modulation of transmitter release. We recently demonstrated that, in nerve terminals of the adult rat cerebral cortex, P2X(7)R activation induced Ca(2+)-dependent vesicular glutamate release and significant Ca(2+)-independent glutamate efflux through the P2X(7)R itself. In the present study, we investigated the effect of the new selective P2X(7)R competitive antagonist 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl) methyl pyridine (A-438079) on cerebrocortical terminal intracellular calcium (intrasynaptosomal calcium concentration; [Ca(2+)](i)) signals and glutamate release, and evaluated whether P2X(7)R immunoreactivity was consistent with these functional tests. A-438079 inhibited functional responses. P2X(7)R immunoreactivity was found in about 45% of cerebrocortical terminals, including glutamatergic and non-glutamatergic terminals. This percentage was similar to that of synaptosomes showing P2X(7)R-mediated [Ca(2+)](i) signals. These findings provide compelling evidence of functional presynaptic P2X(7)R in cortical nerve terminals. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.