A role for Src kinase in the regulation of glutamate release from rat cerebrocortical nerve terminals.
Src tyrosine kinase is widely expressed in the CNS and has been implicated in the regulation of neural excitability and plasticity. In order to investigate the role of Src kinase on neurotransmmiter glutamate release, we studied the effect of PP2, an Src family tyrosine kinase-specific inhibitor, on depolarization-induced glutamate release. PP2 inhibited glutamate release from cerebrocortical synaptosomes stimulated with 3 mM 4AP in a concentration-dependent manner. This inhibitory effect was not result from a decrease in synaptosomal excitability because PP2 did not alter 4AP-evoked depolarization of the synaptosomal plasma membrane potential. In addition, examination of the effect of PP2 on the influx of Ca2+ elicited by 4AP indicated that inhibition of Src activity resulted in an decrease of voltage-dependent Ca2+ influx. These results suggest that protein phosphorylation effected by Src may increase presynaptic Ca2+ channel activity and in so doing enhance evoked glutamate release. Inhibition of Src may represent a neuroprotective effect to limit the release of glutamate.
Wang
Su-Jane
SJ
School of Medicine, Fu Jen Catholic University, 510 Chung-Cheng Road, Hsin-Chuang, Taipei Hsien, Taiwan 24205. med0003@fju.edu.tw
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D019833:Genistein / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D018698:Glutamic Acid; D015761:4-Aminopyridine; D019833:Genistein; D019061:src-Family Kinases; D002118:Calcium; D016257:Fura-2