Jak2 and Ca2+/calmodulin are key intermediates for bradykinin B-2 receptor-mediated activation of Na+/H+ exchange in KNRK and CHO cells
(2003) In Assay and Drug Development Technologies 1(2). p.281-289- 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 beta(2) receptor to activate Na+/H+ exchange in two cell lines, KNRK and CHO. In both cell types, beta(2) 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 beta(2)... (More)
- 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 beta(2) receptor to activate Na+/H+ exchange in two cell lines, KNRK and CHO. In both cell types, beta(2) 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 beta(2) receptor antagonist HOE140, but not by the beta(1) receptor antagonist des-Arg(10)-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 (beta(2) receptor --> Jak2 --> CAM --> Na+/H+ exchanger) is a fundamental regulator of Na+/H+ exchange activity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/296578
- author
- Lefler, D ; Mukhin, YV ; Pettus, T ; Leeb-Lundberg, Fredrik LU ; Garnovskaya, MN and Raymond, JR
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Assay and Drug Development Technologies
- volume
- 1
- issue
- 2
- pages
- 281 - 289
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- pmid:15090193
- wos:000186310700007
- scopus:4344637075
- pmid:15090193
- ISSN
- 1540-658X
- DOI
- 10.1089/15406580360545099
- language
- English
- LU publication?
- yes
- id
- a8a7734e-8bc2-4b59-b52d-287d84d7a356 (old id 296578)
- date added to LUP
- 2016-04-01 12:18:01
- date last changed
- 2022-02-03 20:17:59
@article{a8a7734e-8bc2-4b59-b52d-287d84d7a356, 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 beta(2) receptor to activate Na+/H+ exchange in two cell lines, KNRK and CHO. In both cell types, beta(2) 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 beta(2) receptor antagonist HOE140, but not by the beta(1) receptor antagonist des-Arg(10)-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 (beta(2) receptor --> Jak2 --> CAM --> Na+/H+ exchanger) is a fundamental regulator of Na+/H+ exchange activity.}}, author = {{Lefler, D and Mukhin, YV and Pettus, T and Leeb-Lundberg, Fredrik and Garnovskaya, MN and Raymond, JR}}, issn = {{1540-658X}}, language = {{eng}}, number = {{2}}, pages = {{281--289}}, publisher = {{Mary Ann Liebert, Inc.}}, series = {{Assay and Drug Development Technologies}}, title = {{Jak2 and Ca2+/calmodulin are key intermediates for bradykinin B-2 receptor-mediated activation of Na+/H+ exchange in KNRK and CHO cells}}, url = {{http://dx.doi.org/10.1089/15406580360545099}}, doi = {{10.1089/15406580360545099}}, volume = {{1}}, year = {{2003}}, }