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Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells.
Mol Cells. 2006 Feb 28; 21(1):42-51.MC

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16511346

Citation

Song, Hyun Ju, et al. "Sphingosine 1-phosphate-induced Signal Transduction in Cat Esophagus Smooth Muscle Cells." Molecules and Cells, vol. 21, no. 1, 2006, pp. 42-51.
Song HJ, Choi TS, Chung FY, et al. Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells. Mol Cells. 2006;21(1):42-51.
Song, H. J., Choi, T. S., Chung, F. Y., Park, S. Y., Ryu, J. S., Woo, J. G., Min, Y. S., Shin, C. Y., & Sohn, U. D. (2006). Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells. Molecules and Cells, 21(1), 42-51.
Song HJ, et al. Sphingosine 1-phosphate-induced Signal Transduction in Cat Esophagus Smooth Muscle Cells. Mol Cells. 2006 Feb 28;21(1):42-51. PubMed PMID: 16511346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine 1-phosphate-induced signal transduction in cat esophagus smooth muscle cells. AU - Song,Hyun Ju, AU - Choi,Tai Sik, AU - Chung,Fa Yong, AU - Park,Sun Young, AU - Ryu,Jung Soo, AU - Woo,Jae Gwang, AU - Min,Young Sil, AU - Shin,Chang Yell, AU - Sohn,Uy Dong, PY - 2006/3/3/pubmed PY - 2006/4/14/medline PY - 2006/3/3/entrez SP - 42 EP - 51 JF - Molecules and cells JO - Mol. Cells VL - 21 IS - 1 N2 - 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. SN - 1016-8478 UR - https://www.unboundmedicine.com/medline/citation/16511346/Sphingosine_1_phosphate_induced_signal_transduction_in_cat_esophagus_smooth_muscle_cells_ L2 - http://www.molcells.org/journal/view.html?year=2006&volume=21&number=1&spage=42 DB - PRIME DP - Unbound Medicine ER -