A-kinase Anchoring Protein Mediates TRPV1 Thermal Hyperalgesia Through PKA Phosphorylation of TRPV1

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2008 Apr 3

PMID 18381233

Citations 77

Authors

Nathaniel A Jeske

Anibal Diogenes

Nikita B Ruparel

Jill C Fehrenbacher

Michael Henry

Armen N Akopian

Kenneth M Hargreaves

Affiliations

Soon will be listed here.

Abstract

Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.

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