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The signaling mechanism of the sphingosylphosphorylcholine-induced contraction in cat esophageal smooth muscle cells

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  • Drug efficacy and safety
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Abstract

We investigated the signaling pathway on sphingosinephosphorylcholine (SPC) -induced contraction in cat esophageal smooth muscle cells. SPC induced in a dose-dependent manner contractile effect. We have previously shown that lysophospholipid (LPL) receptor subtypes including the S1P1, S1P2, S1P3, and S1P5 receptor are present in esophageal smooth muscle. Only EDG-5 (S1P2) receptor antibody penetration into permeablilized cells inhibited the SPC-induced contraction. Pertussis toxin (PTX) and specific antibodies to Gi1, Gi2, Gi3 and Go inhibited the contraction, implying that SPC-induced contraction depends on PTX-sensitive Gi1, Gi2, Gi3, and Go protein. A phospholipase inhibitor U73122 and incubation of permeabilized cells with PLC-β3 antibody inhibited SPC-induced contraction. The PKC-mediated contraction may be isozyme specific since only PKCε antibody inhibited the contraction. Preincubation with MEK inhibitor PD98059 blocked the SPC-induced contraction, but p38 MAPK inhibitor SB202190 did not. Cotreatment with GF109203X and PD98059 did not show synergistic effects, suggesting that these two kinases are involved in the same signaling pathway in the SPC-induced contraction. The data suggest that S1P-induced contraction in feline esophageal smooth muscle cells depends on activation of the Gi1, Gi2, Gi3 and Go proteins and the PLCβ3 isozyme via the S1P2 receptor, leading to stimulation of a PKCε pathway, which subsequently activates a p44/p42 MAPK pathway.

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Abbreviations

pCMB:

p-chloromercuribenzoic acid

DEDA:

dimethyl-eicosadienoic acid

EDG:

endothelial differentiation gene

ERK:

extracellular signal-regulated protein kinases

MAPK:

mitogen-activated protein kinase

PKC:

protein kinase C

PLC:

phospholipase C

PLD:

phospholipase D

LA2 :

phospholipase A2

PTX:

pertussis toxin

SPC:

sphingosinephosphoryl-choline

SDS:

sodium dodecyl sulfate

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Authors and Affiliations

  1. Korea Ginseng Institute, Chung Ang University, 456-756, Ansung, Gyungki

    Byung Ok Im

  2. Department of Oriental Medical Food & Nutrition, Semyung University, 390-711, Jecheon, Choongbuk, Korea

    Sung Kwon Ko

  3. College of Pharmacy, Chung Ang University, 156-756, Seoul, Korea

    Yong Sung Kim, Hyun Ju Song, Sun Young Park, Young Sil Min, Wan Kyun Whang & Uy Dong Sohn

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  1. Yong Sung Kim
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  2. Hyun Ju Song
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  3. Sun Young Park
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Kim, Y.S., Song, H.J., Park, S.Y. et al. The signaling mechanism of the sphingosylphosphorylcholine-induced contraction in cat esophageal smooth muscle cells. Arch Pharm Res 30, 1608–1618 (2007). https://doi.org/10.1007/BF02977331

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