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Novel Mechanisms of Activation of Endothelial Nitric Oxide Synthase Mediated by Endothelial Transient Receptor Potential Vanilloid Type 1
Author(s) -
Ching LiChieh,
Kou Yu Ru,
Pan ChingChian,
Lee TzongShyuan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.984.2
Subject(s) - trpv1 , enos , chemistry , phosphorylation , protein kinase b , capsazepine , microbiology and biotechnology , transient receptor potential channel , calmodulin , medicine , nitric oxide , endocrinology , nitric oxide synthase , receptor , biochemistry , biology , organic chemistry , enzyme
OBJECTIVE We investigated the molecular mechanism underlying the role of transient receptor potential vanilloid type 1 (TRPV1) in the activation of endothelial NO synthase (eNOS) in endothelial cells (ECs) and mice. METHODES AND RESULTS In bovine aortic ECs, TRPV1 ligands (evodiamine or capsaicin) promoted NO production, eNOS phosphorylation and TRPV1‐eNOS interaction, all of which were abrogated by the TRPV1 antagonist capsazepine and extracellular Ca 2+ remove. TRPV1 ligands also enhanced the phosphorylation of Akt, calmodulin‐dependent protein kinase II (CaMKII) and TRPV1, and increased interactions of TRPV1 with Akt and CaMKII. Inhibition of PI3K and CaMKII suppressed ligand‐induced increases in TRPV1 phosphorylation, TRPV1‐eNOS interaction and eNOS activation. In vivo experiemnts revealed that TRPV1 activation increased the phosphorylation of Akt, CaMKII and eNOS in the aortas of wild type mice, whereas it failed to activate eNOS in the aortas of TRPV1 deficient mice. CONCLUSION TRPV1 activation in ECs may trigger a Ca 2+ ‐dependant PI3K/Akt/CaMKII signaling leading to enhanced phosphorylation of TRPV1, increased TRPV1‐eNOS interaction and ultimmately eNOS activation. Thus, in addition to its channel function, the TRPV1 may possess a potential role serving as a scaffold for recruitment and interaction with eNOS, Akt and CaMKII, which may be vital for regulating eNOS activation.