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http://purl.uniprot.org/citations/21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21705673http://www.w3.org/2000/01/rdf-schema#comment"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 TRPV4-dependent calcium influx is mediated through a receptor-operated pathway. Furthermore, we found that ACh treatment activated protein kinase C (PKC) α, and inhibition of PKCα activity by the specific inhibitor Go-6976, or expression of a kinase-dead mutant of PKCα but not PKCε or downregulation of PKCα expression by chronic 12-O-tetradecanoylphorbol-13-acetate treatment, completely abolished ACh-induced calcium influx. Finally, we found that ACh-induced vasodilation was inhibited by the PKCα inhibitor Go-6976 in small mesenteric arteries from wild-type mice, but not in TRPV4 null mice. Taken together, these findings demonstrate, for the first time, that a specific isoform of PKC, PKCα, mediates agonist-induced receptor-mediated TRPV4 activation in endothelial cells."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.org/dc/terms/identifier"doi:10.1152/ajpheart.00142.2011"xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Suzuki M."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Zhang D.X."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Meszaros J.G."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Bratz I.N."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Thodeti C.K."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Adapala R.K."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/author"Talasila P.K."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/name"Am J Physiol Heart Circ Physiol"xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/pages"H757-65"xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/title"PKCalpha mediates acetylcholine-induced activation of TRPV4-dependent calcium influx in endothelial cells."xsd:string
http://purl.uniprot.org/citations/21705673http://purl.uniprot.org/core/volume"301"xsd:string
http://purl.uniprot.org/citations/21705673http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21705673
http://purl.uniprot.org/citations/21705673http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21705673
http://purl.uniprot.org/uniprot/#_D3Z1H6-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_D3Z1H7-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_E9Q7L7-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_Q3TYG5-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_Q4VA93-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_P20444-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_Q3TQ39-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673
http://purl.uniprot.org/uniprot/#_Q9EPK8-mappedCitation-21705673http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21705673