PMID- 18381233 OWN - NLM STAT- MEDLINE DCOM- 20090421 LR - 20220318 IS - 1872-6623 (Electronic) IS - 0304-3959 (Print) IS - 0304-3959 (Linking) VI - 138 IP - 3 DP - 2008 Sep 15 TI - A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. PG - 604-616 LID - 10.1016/j.pain.2008.02.022 [doi] 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. FAU - Jeske, Nathaniel A AU - Jeske NA AD - Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center of San Antonio, MC 7908, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA Department of Endodontics, University of Texas Health Science Center of San Antonio, San Antonio, TX, USA Department of Cellular and Structural Biology, University of Texas Health Science Center of San Antonio, San Antonio, TX, USA Department of Pharmacology, University of Texas Health Science Center of San Antonio, San Antonio, TX, USA. FAU - Diogenes, Anibal AU - Diogenes A FAU - Ruparel, Nikita B AU - Ruparel NB FAU - Fehrenbacher, Jill C AU - Fehrenbacher JC FAU - Henry, Michael AU - Henry M FAU - Akopian, Armen N AU - Akopian AN FAU - Hargreaves, Kenneth M AU - Hargreaves KM LA - eng GR - DE13942/DE/NIDCR NIH HHS/United States GR - DE016500/DE/NIDCR NIH HHS/United States GR - F32 DE016500-02/DE/NIDCR NIH HHS/United States GR - F32 DE016500/DE/NIDCR NIH HHS/United States GR - DA19585/DA/NIDA NIH HHS/United States GR - R01 DA019585/DA/NIDA NIH HHS/United States GR - R01 DE013942/DE/NIDCR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080401 PL - United States TA - Pain JT - Pain JID - 7508686 RN - 0 (A Kinase Anchor Proteins) RN - 0 (Akap5 protein, rat) RN - 0 (RNA, Small Interfering) RN - 0 (TRPV Cation Channels) RN - 0 (TRPV1 receptor) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - A Kinase Anchor Proteins/deficiency/genetics/*metabolism/physiology MH - Animals MH - CHO Cells MH - Cells, Cultured MH - Cricetinae MH - Cricetulus MH - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism MH - Guinea Pigs MH - Hyperalgesia/enzymology/*metabolism MH - Neurons/enzymology/metabolism MH - Phosphorylation MH - RNA, Small Interfering/physiology MH - Rats MH - TRPV Cation Channels/antagonists & inhibitors/genetics/*metabolism MH - Trigeminal Ganglion/cytology/enzymology/metabolism PMC - PMC2593399 MID - NIHMS71597 EDAT- 2008/04/03 09:00 MHDA- 2009/04/22 09:00 PMCR- 2009/09/15 CRDT- 2008/04/03 09:00 PHST- 2007/09/24 00:00 [received] PHST- 2007/12/17 00:00 [revised] PHST- 2008/02/20 00:00 [accepted] PHST- 2008/04/03 09:00 [pubmed] PHST- 2009/04/22 09:00 [medline] PHST- 2008/04/03 09:00 [entrez] PHST- 2009/09/15 00:00 [pmc-release] AID - 00006396-200809150-00017 [pii] AID - 10.1016/j.pain.2008.02.022 [doi] PST - ppublish SO - Pain. 2008 Sep 15;138(3):604-616. doi: 10.1016/j.pain.2008.02.022. Epub 2008 Apr 1.