Role of a Tyrosine Kinase in the Co2-induced Stimulation of Hco3- Reabsorption by Rabbit S2 Proximal Tubules.
From: Dept. of Cellular and Molecular Physiology, Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06520, USA.
American journal of physiology. Renal physiology
- Publish Date: Aug 2006
- ISSN: 0363-6127
- Volume: 291
- Issue: 2
- Pages: F358-67
- Medium: Print
- Language: English
- Citation (JAMA): Zhou Yuehan, Bouyer Patrice, Boron Walter F, et al. Role of a Tyrosine Kinase in the Co2-induced Stimulation of Hco3- Reabsorption by Rabbit S2 Proximal Tubules.. Am. J. Physiol. Renal Physiol. Aug 2006;291:F358-67
Abstract
A previous study demonstrated that proximal tubule cells regulate HCO(3)(-) reabsorption by sensing acute changes in basolateral CO(2) concentration, suggesting that there is some sort of CO(2) sensor at or near the basolateral membrane (Zhou Y, Zhao J, Bouyer P, and Boron WF Proc Natl Acad Sci USA 102: 3875-3880, 2005). Here, we hypothesized that an early element in the CO(2) signal-transduction cascade might be either a receptor tyrosine kinase (RTK) or a receptor-associated (or soluble) tyrosine kinase (sTK). In our experiments, we found, first, that basolateral 17.5 microM genistein, a broad-spectrum tyrosine kinase inhibitor, virtually eliminates the CO(2) sensitivity of HCO(3)(-) absorption rate (J(HCO(3))). Second, we found that neither basolateral 250 nM nor basolateral 2 microM PP2, a high-affinity inhibitor for the Src family that also inhibits the Bcr-Abl sTK as well as the Kit RTK, reduces the CO(2)-stimulated increase in J(HCO(3)). Third, we found that either basolateral 35 nM PD168393, a high-affinity inhibitor of RTKs in the erbB (i.e., EGF receptor) family, or basolateral 10 nM BPIQ-I, which blocks erbB RTKs by competing with ATP, eliminates the CO(2) sensitivity. In conclusion, the transduction of the CO(2) signal requires activation of a tyrosine kinase, perhaps an erbB. The possibilities include the following: 1) a TK is simply permissive for the effect of CO(2) on J(HCO(3)); 2) a CO(2) receptor activates an sTK, which would then raise J(HCO(3)); 3) a CO(2) receptor transactivates an RTK; and 4) the CO(2) receptor could itself be an RTK.
Mesh Headings (Keywords): Absorption, Animals, Bicarbonates, Carbon Dioxide, Dimethyl Sulfoxide, Enzyme Inhibitors, Female, Genistein, Imidazoles, Kidney Tubules, Proximal, Protein-Tyrosine Kinases, Pyrimidines, Quinazolines, Rabbits, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 16705143
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.