PKCalpha mediates acetylcholine-induced activation of TRPV4-dependent calcium influx in endothelial cells.

Title

PKCalpha mediates acetylcholine-induced activation of TRPV4-dependent calcium influx in endothelial cells.

Creator

Adapala Ravi K; Talasila Phani K; Bratz Ian N; Zhang David X; Suzuki Makoto; Meszaros J Gary; Thodeti Charles K

Publisher

American journal of physiology. Heart and circulatory physiology

Date

2011
2011-09

Description

Transient receptor potential vanilloid channel 4 (TRPV4) is a polymodally activated nonselective cationic channel implicated in the regulation of vasodilation and hypertension. We and others have recently shown that cyclic stretch and shear stress activate TRPV4-mediated calcium influx in endothelial cells (EC). In addition to the mechanical forces, acetylcholine (ACh) was shown to activate TRPV4-mediated calcium influx in endothelial cells, which is important for nitric oxide-dependent vasodilation. However, the molecular mechanism through which ACh activates TRPV4 is not known. Here, we show that ACh-induced calcium influx and endothelial nitric oxide synthase (eNOS) phosphorylation but not calcium release from intracellular stores is inhibited by a specific TRPV4 antagonist, AB-159908. Importantly, activation of store-operated calcium influx was not altered in the TRPV4 null EC, suggesting that

Subject

Acetylcholine/*pharmacology; Animals; Calcium Signaling/*drug effects; Carbazoles/pharmacology; Cells; Cultured; Endothelial Cells/*drug effects/enzymology; Enzyme Activation; Inbred C57BL; Knockout; Male; Mesenteric Arteries/drug effects/enzymology; Mice; Mutation; Nitric Oxide Synthase Type III/metabolism; Phosphorylation; Protein Kinase C-alpha/genetics/*metabolism; Protein Kinase Inhibitors/pharmacology; Tetradecanoylphorbol Acetate/pharmacology; Time Factors; Transfection; TRPV Cation Channels/*agonists/deficiency/genetics/metabolism; Vasodilation/*drug effects; Vasodilator Agents/*pharmacology

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

H757–765

Issue

3

Volume

301

Citation

Adapala Ravi K; Talasila Phani K; Bratz Ian N; Zhang David X; Suzuki Makoto; Meszaros J Gary; Thodeti Charles K, “PKCalpha mediates acetylcholine-induced activation of TRPV4-dependent calcium influx in endothelial cells.,” NEOMED Bibliography Database, accessed July 26, 2021, https://neomed.omeka.net/items/show/4596.

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