Responses to sphingosine-1-phosphate in X. laevis oocytes: similarities with lysophosphatidic acid signaling.
Sphingosine-1-phosphate (S1P, 50 microM) induces inward currents in Xenopus laevis oocytes voltage clamped at -70 mV. The currents are Ca(2+)-activated Cl- currents, as shown by a reversal potential of -20 mV and absence of the response after intracellular injection of ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 10 mM). The response is nearly indistinguishable from that to the related compound lysophosphatidic acid (LPA), and complete cross-desensitization occurs between LPA and S1P responses. Both the LPA and S1P responses are inhibited by suramin (2 mM) and dithiothreitol (5 mM). These responses appear mediated by a specific membrane receptor, since intracellular injection of S1P (5 microM) does not induce currents, and sphingosine and the related compounds sphingosylphosphorylcholine and N,N-dimethylsphingosine, all at 100 microM, neither induce currents nor block the response to S1P. HEK-293 and COS-1 cells respond with intracellular Ca2+ release to both 50 microM S1P and 10 microM LPA; K-562 cells do not. No cross-desensitization was noted in the responsive cells. Our findings indicate that S1P and LPA might act through the same mechanism, probably a membrane receptor.
Durieux
M E
ME
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville.
Carlisle
S J
SJ
Salafranca
M N
MN
Lynch
K R
KR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014982:Xenopus laevis
D018118:Chloride Channels; D007473:Ion Channels; D008246:Lysophospholipids; D008565:Membrane Proteins; C060506:sphingosine 1-phosphate; D004533:Egtazic Acid; D013110:Sphingosine; D002118:Calcium