부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1113/jphysiol.2008.158709 Byline: Hidetada Matsuoka (1), Keita Harada (1), Yutaka Endo (1), Akira Warashina (14), Yoshiaki Doi (2), Jun Nakamura (3), Masumi Inoue (1) Abstract: GABA is known to produce membrane depolarization and secretion in adrenal medullary (AM) cells in various species. However, whether the GABAergic system is intrinsic or extrinsic or both in the adrenal medulla and the role that GABA plays are controversial. Therefore, these issues were addressed by combining a biochemical and functional analysis. Glutamic acid decarboxylase (GAD), a GABA synthesizing enzyme, and vesicular GABA transporter (VGAT) were expressed in rat AM cells at the mRNA and protein levels, and the adrenal medulla had no nerve fibre-like structures immunoreactive to an anti-GAD Ab. The double staining for VGAT and chromogranin A indicates that GABA was stored in chromaffin granules. The [alpha]1, [alpha]3, [beta]2/3, [gamma]2 and [delta] subunits of GABA.sub.A receptors were identified in AM cells at the mRNA and protein levels. Pharmacological properties of GABA-induced Cl.sup.- currents, immunoprecipitation experiments and immunocytochemistry indicated the expression of not only [gamma]2-, but also [delta]-containing GABA.sub.A receptors, which have higher affinities for GABA and neurosteroids. Expression of GATs, which are involved in the clearance of GABA at GABAergic synapses, were conspicuously suppressed in the adrenal medulla, compared with expression levels of GABA.sub.A receptors. Increases in Ca.sup.2+ signal in AM cells evoked trans-synaptically by nerve stimulation were suppressed during the response to GABA, and this suppression was attributed to the shunt effect of the GABA-induced increase in conductance. Overall Ca.sup.2+ responses to electrical stimulation and GABA in AM cells were larger or smaller than those to electrical stimulation alone, depending on the frequency of stimulation. The results indicate that GABA functions as a paracrine in rat AM cells and this function may be supported by the suppression of GAT expression and the expression of not only [gamma]2-, but also [delta]-GABA.sub.A receptors. Author Affiliation: (1)Cell and Systems Physiology (2)Anatomy (3)Psychiatry, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan (4)Section of Cell Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan Article History: (Received 24 June 2008; accepted after revision 27 August 2008; first published online 28 August 2008) Article note: Corresponding author M. Inoue: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan. Email: minoue@med.uoeh-u.ac.jp