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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-3-2
pubmed:abstractText
We investigated the mechanism of contraction induced by S1P in esophageal smooth muscle cells. Western blot analysis demonstrated that S1P(1), S1P(2), S1P(3), and S1P(5) receptors existed in the cat esophagus. Only penetration of EDG-5 (S1P(2)) antibody into permeabilized cells inhibited S1P-induced contraction. Pertussis toxin (PTX) also inhibited contraction, suggesting that it was mediated by S1P(2) receptors coupled to a PTX-sensitive G(i) protein. Specific antibodies to G(i2), G(q) and G(beta) inhibited contraction, implying that the S1P-induced contraction depends on PTX-insensitive G(q) and G(beta) dimers as well as the PTX-sensitive G(i2). Contraction was not affected by the phospholipase A2 inhibitor DEDA, or the PLD inhibitor rho-chloromer-curibenzoate, but it was abolished by the PLC inhibitor U73122. Incubation of permeabilized cells with PLCb3 antibody also inhibited contraction. Contraction involved the activation of a PKC pathway since it was affected by GF109203X and chelerythrine. Since PKCepsilon antibody inhibited contraction, PKCe may be required. Preincubation of the muscle cells with the MEK inhibitor PD98059 blocked S1P-induced contraction, but the p38 MAP kinase inhibitor SB202190 did not. In addition, co-treatment of cells with GF 109203X and PD98059 did not have a synergistic effect, suggesting that these two kinases are involved in the same signaling pathway. Our data suggest that S1P-induced contraction in esophageal smooth muscle cells is mediated by S1P(2) receptors coupled to PTX-sensitive G(i2) proteins, and PTX-insensitive G(q) and G(beta) proteins, and that the resulting activation of the PLCb3 and PKCepsilon pathway leads to activation of a p44/p42 MAPK pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1016-8478
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16511346-Animals, pubmed-meshheading:16511346-Cats, pubmed-meshheading:16511346-Dose-Response Relationship, Drug, pubmed-meshheading:16511346-Esophagus, pubmed-meshheading:16511346-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:16511346-Lysophospholipids, pubmed-meshheading:16511346-MAP Kinase Kinase Kinases, pubmed-meshheading:16511346-Mitogen-Activated Protein Kinases, pubmed-meshheading:16511346-Models, Biological, pubmed-meshheading:16511346-Muscle Contraction, pubmed-meshheading:16511346-Myocytes, Smooth Muscle, pubmed-meshheading:16511346-Protein Kinase C, pubmed-meshheading:16511346-Receptors, Lysosphingolipid, pubmed-meshheading:16511346-Signal Transduction, pubmed-meshheading:16511346-Sphingosine, pubmed-meshheading:16511346-Time Factors, pubmed-meshheading:16511346-Type C Phospholipases
pubmed:year
2006
pubmed:articleTitle
Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells.
pubmed:affiliation
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't