Functional evidence for presynaptic P2X7 receptors in adult rat cerebrocortical nerve terminals.
The presynaptic P2X7 receptor (P2X7R) plays an important role in the modulation of transmitter release. We recently demonstrated that, in nerve terminals of the adult rat cerebral cortex, P2X7R activation induced Ca2+-dependent vesicular glutamate release and significant Ca2+-independent glutamate efflux through the P2X7R 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;[Ca2+](i) signals and glutamate release, and evaluated whether P2X7R immunoreactivity was consistent with these functional tests. A-438079 inhibited functional responses. P2X7R immunoreactivity was found in about 45% of cerebrocortical terminals, including glutamatergic and non-glutamatergic terminals. This percentage was similar to that of synaptosomes showing P2X7R-mediated [Ca2+]i signals. These findings provide compelling evidence of functional presynaptic P2X7R in cortical nerve terminals.
Alloisio
Susanna
S
Institute of Biophysics, CNR, Via De Marini, 6 - 16149 Genoa, Italy.
Cervetto
Chiara
C
Passalacqua
Mario
M
Barbieri
Raffaella
R
Maura
Guido
G
Nobile
Mario
M
Marcoli
Manuela
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles