부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1471-4159.2008.05560.x Byline: Jun-Wei Zeng (1), Xiao-Hong Liu (1,2), Jin-Hai Zhang, Xi-Gui Wu, Huai-Zhen Ruan Keywords: astrocyte; Ca; glutamate release; P2Y receptor; spinal cord Abstract: Abstract P2 receptors have been implicated in the release of neurotransmitter and proinflammatory cytokines by the response to neuroexcitatory substances in astrocytes. In the present study, we examined the mechanisms of ADP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS, ADP analogue) on glutamate release from cultured dorsal spinal cord astrocytes by using confocal laser scanning microscopy and HPLC. Immunofluorescence activity showed that P2Y.sub.1 receptor protein is expressed in cultured astrocytes. ADP and ADPbetaS-induced [Ca.sup.2+].sub.i increase and glutamate release are mediated by P2Y.sub.1 receptor. Ca.sup.2+ release from IP.sub.3-sensitive calcium stores and protein kinase C (PKC) activation is important for glutamate release from astrocytes. Furthermore, P2Y.sub.1 receptor-evoked glutamate release is regulated by volume-sensitive Cl.sup.- channels and anion co-transporter, which open up the possibility that P2Y.sub.1 receptor activation causes the increase of cell volume. Release of glutamate by ADPbetaS was abolished by 5-nitro-2 (3-phenyl propy lamino)-benzoate plus furosemide but was unaffected by botulinum toxin A. These observations indicate that P2Y.sub.1 receptor-evoked glutamate may be mediated via volume-sensitive Cl.sup.- channel but not via exocytosis of glutamate containing vesicles. We speculate that P2Y.sub.1 receptors-evoked glutamate efflux, occurring under pathological condition, may modulate the activity of synapses in spinal cord. Article History: Received May 30, 2008; revised manuscript received June 16, 2008; accepted June 17, 2008. Article note: Address correspondence and reprint requests to Dr Huai-Zhen Ruan, Department of Neurobiology, Third Military Medical University, Chongqing 400038, China. E-mail: hzruan61@yahoo.com