Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-6-22
pubmed:abstractText
TRPC6 is a non-voltage-gated Ca(2+) entry/depolarization channel associated with vascular tone regulation and remodeling. Expressed TRPC6 channel responds to both neurohormonal and mechanical stimuli, the mechanism for which remains controversial. In this study, we examined the possible interactions of receptor and mechanical stimulations in activating this channel using the patch clamp technique. In HEK293 cells expressing TRPC6, application of mechanical stimuli (hypotonicity, shear, 2,4,6-trinitrophenol) caused, albeit not effective by themselves, a prominent potentiation of cationic currents (I(TRPC6)) induced by a muscarinic receptor agonist carbachol. This effect was insensitive to a tarantula toxin GsMTx-4 (5 mumol/L). A similar extent of mechanical potentiation was observed after activation of I(TRPC6) by GTPgammaS or a diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG). Single TRPC6 channel activity evoked by carbachol was also enhanced by a negative pressure added in the patch pipette. Mechanical potentiation of carbachol- or OAG-induced I(TRPC6) was abolished by small interfering RNA knockdown of cytosolic phospholipase A(2) or pharmacological inhibition of omega-hydroxylation of arachidonic acid into 20-HETE (20-hydroxyeicosatetraenoic acid). Conversely, direct application of 20-HETE enhanced both OAG-induced macroscopic and single channel TRPC6 currents. Essentially the same results were obtained for TRPC6-like cation channel in A7r5 myocytes, where its activation by noradrenaline or Arg8 vasopressin was greatly enhanced by mechanical stimuli via 20-HETE production. Furthermore, myogenic response of pressurized mesenteric artery was significantly enhanced by weak receptor stimulation dependently on 20-HETE production. These results collectively suggest that simultaneous operation of receptor and mechanical stimulations may synergistically amplify transmembrane Ca(2+) mobilization through TRPC6 activation, thereby enhancing the vascular tone via phospholipase C/diacylglycerol and phospholipase A(2)/omega-hydroxylase/20-HETE pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/20-hydroxy-5,8,11,14-eicosatetraenoi..., http://linkedlifedata.com/resource/pubmed/chemical/Alkane 1-Monooxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Carbachol, http://linkedlifedata.com/resource/pubmed/chemical/Cholinergic Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/MTx4 protein, Grammostola spatulata, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic, http://linkedlifedata.com/resource/pubmed/chemical/Spider Venoms, http://linkedlifedata.com/resource/pubmed/chemical/TRPC Cation Channels, http://linkedlifedata.com/resource/pubmed/chemical/TRPC6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trrp6 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1399-409
pubmed:dateRevised
2011-9-20
pubmed:meshHeading
pubmed-meshheading:19443836-Alkane 1-Monooxygenase, pubmed-meshheading:19443836-Animals, pubmed-meshheading:19443836-Carbachol, pubmed-meshheading:19443836-Cell Line, pubmed-meshheading:19443836-Cholinergic Agonists, pubmed-meshheading:19443836-Dose-Response Relationship, Drug, pubmed-meshheading:19443836-Humans, pubmed-meshheading:19443836-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:19443836-Hydroxylation, pubmed-meshheading:19443836-Male, pubmed-meshheading:19443836-Mechanotransduction, Cellular, pubmed-meshheading:19443836-Muscle Cells, pubmed-meshheading:19443836-Peptides, pubmed-meshheading:19443836-Phospholipases A2, pubmed-meshheading:19443836-Rats, pubmed-meshheading:19443836-Rats, Sprague-Dawley, pubmed-meshheading:19443836-Receptors, Muscarinic, pubmed-meshheading:19443836-Spider Venoms, pubmed-meshheading:19443836-TRPC Cation Channels, pubmed-meshheading:19443836-Type C Phospholipases
pubmed:year
2009
pubmed:articleTitle
Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/omega-hydroxylase/20-HETE pathways.
pubmed:affiliation
Department of Physiology, Graduate School of Medical Sciences, Fukuoka University, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan. inouery@fukuoka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't