Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4329359 | Brain Research | 2008 | 10 Pages |
Abstract
Galanin (GAL), a 29-amino-acid neuropeptide, is involved in various neuronal functions, including the regulation of food intake, hormone secretion and central cardiovascular regulation. The nucleus tractus solitarius (NTS) is known to plays a major role in the regulation of cardiovascular, respiratory, gustatory, hepatic and swallowing functions. Voltage-dependent Ca2+ channels (VDCCs) serve as crucial mediators of membrane excitability and Ca2+-dependent functions such as neurotransmitter release, enzyme activity and gene expression. The purpose of this study was to investigate the effects of GAL on VDCCs currents (ICa) carried by Ba2+ (IBa) in the NTS using patch-clamp recording methods. An application of M617 (GalR1 specific agonist), AR-M961 (GAL receptor GalR 1/2 agonist) and GAL caused inhibition of N- and P/Q-types IBa. M617, GAL, and AR-M961 caused inhibition of IBa in a concentration-dependent manner, with IC50s of 678 nM, 325 nM and 573 nM, respectively. This inhibition was relieved, albeit incompletely, by a depolarizing prepulse. Pretreatment with M35 (GalR non-specific antagonist) attenuated the M617-induced inhibition of IBa. Intracellular dialysis of the Gαi-protein antibody also attenuated the Gal-induced inhibition of IBa. These results indicate that GAL inhibits N- and P/Q-types VDCCs via Gαi-protein βγ subunits mediated by GalR1 in NTS.
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Authors
Takayuki Endoh, Daisuke Sato, Yoshiyuki Wada, Yoshiyuki Shibukawa, Kazuyuki Ishihara, Sadamitsu Hashimoto, Masao Yoshinari, Kenichi Matsuzaka, Masakazu Tazaki, Takashi Inoue,