J Neurosci. 2013 Apr 24;33(17):7407-14. doi: 10.1523/JNEUROSCI.3721-12.2013.

Disrupting sensitization of transient receptor potential vanilloid subtype 1 inhibits inflammatory hyperalgesia.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Fischer, M. J., Btesh, J., McNaughton, P. A.,
["Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom."]
Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel that plays a key role in enhanced pain sensation after inflammation, but directly blocking TRPV1 causes hyperthermia and decreased sensitivity to painful levels of heat in animals and humans. Here we explore an alternative analgesic strategy in which the modulation of TRPV1 is inhibited by antagonizing the interaction between TRPV1 and A kinase anchoring protein 79 (AKAP79), a scaffolding protein essential for positioning serine-threonine kinases adjacent to target phosphorylation sites. We first defined key residues in the domain in TRPV1 that interacts with AKAP79, and we then used this information to construct short peptides capable of preventing TRPV1-AKAP79 interaction. An effective peptide, when coupled to a TAT sequence conferring cell permeability, was found to be analgesic in three mouse models of inflammatory hyperalgesia. These results demonstrate the potential value of interfering with the interaction between TRPV1 and AKAP79 as a novel analgesic strategy.
PMID: 23616546External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Characterization Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 AKAP5/AKAP150 Patch clamp Human 738 ?745 Human Not determined 23616546
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 AKAP5/AKAP150 Co-immunoprecipitation Increase in plasma membrane level 23616546
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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