PP2 inhibits glutamate release from nerve endings by affecting vesicle mobilization
aSchool of Medicine, Fu Jen Catholic University, Hsin-Chuang, Taipei Hsien, Taiwan. Neuroreport
(Impact Factor: 1.52).
12/2005; 16(17):1969-72. DOI: 10.1097/01.wnr.0000189758.57164.85
Src kinase is widely expressed in the brain and its inhibition with PP2 has previously been shown to depress depolarization-evoked glutamate release from rat cerebrocortical synaptosomes by reducing voltage-dependent Ca2+ entry. In this study, we further showed that the inhibitory effect of PP2 on 4-aminopyridine-evoked glutamate release results from a reduction of vesicular exocytosis and not from an inhibition of non-vesicular release. In addition, PP2 significantly inhibited ionomycin-induced or hypertonic sucrose-induced glutamate release. Also, disruption of cytoskeleton organization with cytochalasin D occluded the inhibitory action of PP2 on 4-aminopyridine and ionomycin-evoked glutamate release. These results suggest that PP2-mediated inhibition of glutamate release involves the modulation of some exocytotic steps, possibly through a regulation of actin cytoskeleton dynamics.
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