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J Physiol Volume 568, Number 3, 851-856, November 1, 2005 DOI: 10.1113/jphysiol.2005.095307
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Involvement of Src tyrosine kinase and mitogen-activated protein kinase in the facilitation of calcium channels in rat nucleus of the tractus solitarius by angiotensin II

Takayuki Endoh1

1 Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan

It is recognized that brain contains all the components of the renin–angiotensin systems (RAS). The nucleus of the tractus solitarius (NTS) is known to play 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 angiotensin II (Ang II) on VDCC currents (ICa) in the NTS using patch-clamp recording methods. An application of Ang II caused facilitation of L-type ICa in a concentration-dependent manner with an EC50 of 167 nM and a Hill coefficient of 1.73. AT1 receptor antagonist losartan antagonized the Ang II-induced facilitation of ICa. Intracellular dialysis of the G{alpha}i-protein antibody attenuated the Ang II-induced facilitation of ICa. Both Src tyrosine kinase inhibitor and mitogen-activated protein kinase (MAPK) inhibitor attenuated the Ang II-induced facilitation of ICa. p38 MAPK inhibitor also attenuated the Ang II-induced facilitation of ICa. These results indicate that Ang II facilitates L-type VDCCs via G{alpha}i-proteins involving Src tyrosine kinase and p38 MAPK kinase mediated by AT1 receptors in NTS.

(Received 25 July 2005; accepted after revision 23 August 2005; first published online 25 August 2005)
Corresponding author T. Endoh: Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan. Email: tendoh{at}tdc.ac.jp




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