The signaling mechanism of the sphingosylphosphorylcholine-induced contraction in cat esophageal smooth muscle cells.
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 G(i1), G(i2), G(i3) and G(o) inhibited the contraction, implying that SPC-induced contraction depends on PTX-sensitive G(i1), G(i2), G(i3), and G(o) protein. A phospholipase inhibitor U73122 and incubation of permeabilized cells with PLC-beta3 antibody inhibited SPC-induced contraction. The PKC-mediated contraction may be isozyme specific since only PKCepsilon 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 G(i1), G(i2), G(i3) and G(o) proteins and the PLCbeta3 isozyme via the S1P2 receptor, leading to stimulation of a PKCE pathway, which subsequently activates a p44/p42 MAPK pathway.
Kim
Yong Sung
YS
College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Song
Hyun Ju
HJ
Park
Sun Young
SY
Min
Young Sil
YS
Im
Byung Ok
BO
Ko
Sung Kwon
SK
Whang
Wan Kyun
WK
Sohn
Uy Dong
UD
D000818:Animals; D002415:Cats; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D054799:Phospholipase C beta / Q000502:physiology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D049349:Receptors, Lysosphingolipid / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D049349:Receptors, Lysosphingolipid; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D013110:Sphingosine