title: PP2 inhibits glutamate release from nerve endings by affecting vesicle mobilization.
abstract: 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.
authors.affiliation: aSchool of Medicine, Fu Jen Catholic University, Hsin-Chuang, Taipei Hsien, Taiwan.
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
authors.forename: Guey-Mei
authors.initials: GM
authors.lastname: Jow
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Lee
authors.forename: Su-Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: C412373:AG 1879; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011743:Pyrimidines; D015638:Cytochalasin D; D018698:Glutamic Acid; D019061:src-Family Kinases; D002118:Calcium