A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

Nathaniel A. Jeske; Anibal Diogenes; Nikita B. Ruparel; Jill C. Fehrenbacher; Michael A Henry; Armen N. Akopian; Kenneth M. Hargreaves

doi:10.1016/j.pain.2008.02.022

A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

Nathaniel A. Jeske, Anibal Diogenes, Nikita B. Ruparel, Jill C. Fehrenbacher, Michael A Henry, Armen N. Akopian, Kenneth M. Hargreaves

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

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.

Original language	English (US)
Pages (from-to)	604-616
Number of pages	13
Journal	Pain
Volume	138
Issue number	3
DOIs	https://doi.org/10.1016/j.pain.2008.02.022
State	Published - Sep 15 2008

Keywords

AKAP
Hyperalgesia
PKA
Pain
TRPV1
Trigeminal

ASJC Scopus subject areas

Neurology
Clinical Neurology
Anesthesiology and Pain Medicine

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10.1016/j.pain.2008.02.022

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@article{a8b0df93eff64227845eaedc242bf24a,

title = "A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1",

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.",

keywords = "AKAP, Hyperalgesia, PKA, Pain, TRPV1, Trigeminal",

author = "Jeske, {Nathaniel A.} and Anibal Diogenes and Ruparel, {Nikita B.} and Fehrenbacher, {Jill C.} and Henry, {Michael A} and Akopian, {Armen N.} and Hargreaves, {Kenneth M.}",

note = "Funding Information: We acknowledge Dharshini Amarneethi and Griffin Perry for their excellent technical assistance, David Julius for TRPV1 cDNA, and John D. Scott for AKAP150 cDNAs. These studies were supported by NIH NIDCR DE016500 (N.A.J.), NIH NIDCR DE13942 (M.H.), and NIH NIDA DA19585 (K.M.H.).",

year = "2008",

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doi = "10.1016/j.pain.2008.02.022",

language = "English (US)",

volume = "138",

pages = "604--616",

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TY - JOUR

T1 - A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

AU - Jeske, Nathaniel A.

AU - Diogenes, Anibal

AU - Ruparel, Nikita B.

AU - Fehrenbacher, Jill C.

AU - Henry, Michael A

AU - Akopian, Armen N.

AU - Hargreaves, Kenneth M.

N1 - Funding Information: We acknowledge Dharshini Amarneethi and Griffin Perry for their excellent technical assistance, David Julius for TRPV1 cDNA, and John D. Scott for AKAP150 cDNAs. These studies were supported by NIH NIDCR DE016500 (N.A.J.), NIH NIDCR DE13942 (M.H.), and NIH NIDA DA19585 (K.M.H.).

PY - 2008/9/15

Y1 - 2008/9/15

N2 - 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.

AB - 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.

KW - AKAP

KW - Hyperalgesia

KW - PKA

KW - Pain

KW - TRPV1

KW - Trigeminal

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JO - Pain

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ER -

A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

Abstract

Keywords

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