NEUROPHARMACOLOGY AND NEUROTOXICOLOGYPP2 inhibits glutamate release from nerve endings by affecting vesicle mobilizationShyu, Kou-Gia b; Jow, Guey-Meia; Lee, Yih-Jinga; Wang, Su-JaneaAuthor Information aSchool of Medicine, Fu Jen Catholic University bDivision of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Correspondence and requests for reprints to Dr Su-Jane Wang, PhD, School of Medicine, Fu Jen Catholic University, 510, Chung-Cheng Rd., Hsin-Chuang, Taipei Hsien, Taiwan 24205 Tel: +886 2 29053465; fax: +886 2 29052096; e-mail: [email protected] Sponsorship: This study was supported by grant from the National Science Council of Taiwan, Republic of China (NSC 94-2320-B-030-012) and Shin Kong Wu Ho-Su Memorial Hospital (SKH-FJU-94-05). Received 7 September 2005; revised 27 September 2005; accepted 29 September 2005 NeuroReport: November 28, 2005 - Volume 16 - Issue 17 - p 1969-1972 doi: 10.1097/01.wnr.0000189758.57164.85 Buy Metrics 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. © 2005 Lippincott Williams & Wilkins, Inc.