Premium
TRPA1 and TRPV3 Agonists Increase Intracellular Ca2+ Levels in Native Cerebral Artery Endothelial Cells
Author(s) -
Earley Scott,
Gonzales Albert L.,
Crnich Rachael
Publication year - 2008
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.22.1_supplement.964.17
Subject(s) - extracellular , vasodilation , transient receptor potential channel , endothelial stem cell , nitric oxide , chemistry , intracellular , agonist , stimulation , cerebral arteries , endocrinology , receptor , microbiology and biotechnology , medicine , biochemistry , biology , in vitro
Increases in endothelial cell [Ca 2+ ] initiate the production of vasodilatory factors such as nitric oxide, prostaglandin, and epoxyeicosatrienoic acids. The molecular identities of the ion channels responsible for endothelial cell Ca 2+ entry are not well defined. We examined the hypothesis that members of the transient receptor potential (TRP) superfamily of cation channels serve this function. Using ratiometric Ca 2+ imaging, we examined the effects of the TRPA1 agonist allyl isothiocyanate (AI) and the combined TRPA1/TRPV3 agonists eugenol (EG) and carvacrol (CV) on the intracellular [Ca 2+ ] of freshly dispersed native endothelial cells from rat cerebral arteries. All three agonists stimulated increases in endothelial cell [Ca 2+ ], however, CV was much more potent (EC 50 = 34 μM) than either AI (EC 50 = 400 μM) or EG (EC 50 = 2.3 mM). None of these agonists stimulated increases in endothelial cell [Ca 2+ ] when extracellular Ca 2+ was not present in the bathing solution, suggesting that Ca 2+ influx is required for this response. Additional experiments demonstrated that CV and AI both caused concentration‐dependent dilation of intact, pre‐constricted cerebral arteries. Our findings indicate that stimulation of TRPA1 and/or TRPV3 activity elicits increases in endothelial cell [Ca 2+ ] and cerebral artery dilation, possibly by promoting the production of vasodilatory factors. Supported by AHA0535226N.