| 18602374 |
Endoh T, Sato D, Wada Y, Shibukawa Y, Ishihara K, Hashimoto S, Yoshinari M, Matsuzaka K, Tazaki M, Inoue T: Galanin inhibits calcium channels via Galpha (i)-protein mediated by GalR1 in rat nucleus tractus solitarius. Brain Res. 2008 Sep 10;1229:37-46. Epub 2008 Jun 20.
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 Ca (2+)-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 I (Ba). M617, GAL, and AR-M961 caused inhibition of I (Ba) 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 I (Ba). Intracellular dialysis of the Galpha (i)-protein antibody also attenuated the Gal-induced inhibition of IBa. These results indicate that GAL inhibits N- and P/Q-types VDCCs via Galpha (i)-protein betagamma subunits mediated by GalR1 in NTS. |
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