A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1.
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.
Jeske
Nathaniel A
NA
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.
Diogenes
Anibal
A
Ruparel
Nikita B
NB
Fehrenbacher
Jill C
JC
Henry
Michael
M
Akopian
Armen N
AN
Hargreaves
Kenneth M
KM
D054758:A Kinase Anchor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006168:Guinea Pigs; D006930:Hyperalgesia / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000502:physiology; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
D054758:A Kinase Anchor Proteins; C415703:Akap5 protein, rat; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D017868:Cyclic AMP-Dependent Protein Kinases