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.
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 (I(Ca)) in the NTS using patch-clamp recording methods. An application of Ang II caused facilitation of L-type I(Ca) 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 I(Ca). Intracellular dialysis of the Galpha(i)-protein antibody attenuated the Ang II-induced facilitation of I(Ca). Both Src tyrosine kinase inhibitor and mitogen-activated protein kinase (MAPK) inhibitor attenuated the Ang II-induced facilitation of I(Ca). p38 MAPK inhibitor also attenuated the Ang II-induced facilitation of I(Ca). These results indicate that Ang II facilitates L-type VDCCs via Galpha(i)-proteins involving Src tyrosine kinase and p38 MAPK kinase mediated by AT1 receptors in NTS.
Endoh
Takayuki
T
Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan. tendoh@tdc.ac.jp
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism*
D015220:Calcium Channels; D000804:Angiotensin II; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases