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• W2101093047 abstract "Na+/H+ exchangers are ubiquitous in mammalian cells, carrying out key functions, such as cell volume defense, acid-base homeostasis, and regulation of the cytoskeleton. We used two screening technologies (FLIPR and microphysiometry) to characterize the signal transduction pathway used by the bradykinin B2 receptor to activate Na+/H+ exchange in two cell lines, KNRK and CHO. In both cell types, B2 receptor activation resulted in rapid increases in the rate of proton extrusion that were sodium-dependent and could be blocked by the Na+/H+ exchange inhibitors EIPA and MIA or by replacing extracellular sodium with TMA. Activation of Na+/H+ exchange by bradykinin was concentration-dependent and could be blocked by the selective B2 receptor antagonist HOE140, but not by the B1 receptor antagonist des-Arg10-HOE140. Inhibitors of Jak2 tyrosine kinase (genistein and AG490) and of CAM (W-7 and calmidazolium) attenuated bradykinin-induced activation of Na+/H+ exchange. Bradykinin induced formation of a complex between CAM and Jak2, supporting a regulatory role for Jak2 and CAM in the activation of Na+/H+ exchange in KNRK and CHO cells. We propose that this pathway (B2 receptor → Jak2 → CAM → Na+/H+ exchanger) is a fundamental regulator of Na+/H+ exchange activity." @default.
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• W2101093047 date "2003-04-01" @default.
• W2101093047 modified "2023-09-27" @default.
• W2101093047 title "Jak2 and Ca2+/Calmodulin are Key Intermediates for Bradykinin B2Receptor-Mediated Activation of Na+/H+Exchange in KNRK and CHO Cells" @default.
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• W2101093047 doi "https://doi.org/10.1089/15406580360545099" @default.
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