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Caffeine facilitation of glutamate release from rat cerebral cortex nerve terminals (synaptosomes) through activation protein kinase C pathway: an interaction with presynaptic adenosine A1 receptors.

Wang SJ

School of Medicine, Fu Jen Catholic University, Hsin-Chuang, Taipei Hsien, Taiwan. med0003@mails.fju.edu.tw

The present study used nerve terminals (synaptosomes) isolated from rat cerebral cortex to investigate the relationship between caffeine and 4-aminopyridine (4AP)-evoked endogenous excitatory neurotransmitter glutamate release. Micromolar concentrations of caffeine facilitated 4AP, but not KCl or ionomycin-evoked glutamate release from synaptosomes. This release facilitation resulted from an enhancement of vesicular and nonvesicular release and associated with an increase both in 4AP-evoked depolarization of the synaptosomal plasma membrane potential and in 4AP-evoked increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](C)). In addition, the release facilitation by caffeine was significantly reduced in synaptosomes pretreated with a wide spectrum blocker of N- and P/Q-type Ca(2+) channels, omega-conotoxin MVIIC. Furthermore, protein kinase C (PKC) activator and inhibitor, respectively, superseding or suppressing the caffeine-mediated facilitation of glutamate release. These results concluded that caffeine exerts their presynaptic facilitatory effect, likely through the activation of PKC pathway, which subsequently enhances terminal excitability and Ca(2+) entry to cause an increase in evoked glutamate release from rat cerebrocortical nerve terminals. Additionally, this release facilitation may involve an interaction of caffeine with presynaptic adenosine A1 receptors as adenosine A1 receptor inhibition abolished the caffeine-mediated facilitation of evoked glutamate release.

Published 3 April 2007 in Synapse, 61(6): 401-11.
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