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Am J Physiol Cell Physiol (April 14, 2004). doi:10.1152/ajpcell.00113.2004
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Submitted on February 26, 2004
Accepted on April 5, 2004

Modulation of TRPV1 by non-receptor tyrosine kinase, c-src kinase

Xiaochun Jin1, Nemat Morsy1, John Winston2, Pankaj J Pasricha2, Kennon Garrett1, and Hamid I Akbarali1*

1 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
2 Division of Gastroenterology, University of Texas Medical Branch, Galveston, TX, USA

* To whom correspondence should be addressed. E-mail: hamid-akbarali{at}ouhsc.edu.

The capsaicin receptor, TRPV1, is a non-selective cation channel that is expressed in sensory neurons. In this study, we examined the role of the non-receptor cellular tyrosine kinase, c-src kinase in the modulation of the rat TRPV1. Capsaicin-induced currents in identified colonic DRG neurons were blocked by the c-src kinase inhibitor, PP2 and enhanced by the tyrosine phosphatase inhibitor, sodium orthovandate. PP2 also abolished currents in HEK293 cells transfected with rat TRPV1 while co-transfection of TRPV1 with v-src resulted in 5 fold increase in capsaicin-induced currents. In cells transfected with dominant negative c-src and TRPV1, capsaicin-induced currents were decreased by approximately 4 fold. TRPV1 co-immunoprecipitated with src-kinase and was tyrosine phosphorylated. These studies demonstrate that TRPV1 is a potential target for cellular tyrosine kinase-dependent phosphorylation




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