Modulation of smooth muscle contraction by sphingosylphosphorylcholine.
We have investigated the effect of sphingosylphosphorylcholine (SPC), a synthetic product that was implicated in the sphingomyelin cycle, and have assessed its role in intracellular signaling. SPC induced a dose-dependent contractile effect of smooth muscle cells isolated from the rectosigmoid of the rabbit. Maximal contraction occurred at 10(-6) M. The response started early, 25.4 +/- 6% shortening at 15 s, peaked at 30 s (32.5 +/- 2%), and remained sustained at 8 min (30.0 +/- 3.5%). Preincubation of the cells with thapsigargin had no effect on contraction induced by SPC. The response to a combination of threshold concentrations of inositol 1,4,5-trisphosphate (IP3) and SPC was additive and was significantly different from the maximal response elicited by each agent alone. SPC also induced activation of mitogen-activated protein kinase (MAP kinase). This study demonstrates that SPC is important in cellular signaling of gastrointestinal smooth muscle cells through a mechanism that is independent of IP3-sensitive calcium release and probably through activation of a protein kinase C-mediated activation of MAP kinase.
Bitar
K N
KN
Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109, USA.
Yamada
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism; D004064:Digestive System / Q000166:cytology; D004068:Digestive System Physiological Phenomena; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005769:Gastrointestinal Motility / Q000187:drug effects*; D015151:Immunoblotting; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013110:Sphingosine; D002118:Calcium