RESPONSES TO SPHINGOSINE-1-PHOSPHATE IN X-LAEVIS OOCYTES - SIMILARITIES WITH LYSOPHOSPHATIDIC ACID SIGNALING

Sphingosine-1-phosphate (S1P, 50 muM) induces inward currents in Xenopus laevis oocytes voltage clamped at -70 mV. The currents are Ca2+-activated Cl- currents, as shown by a reversal potential of -20 mV and absence of the response after intracellular injection of ethylene glycol-bis(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 SIP 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 muM) does not induce currents, and sphingosine and the related compounds sphingosylphosphorylcholine and N,N-dimethylsphingosine, all at 100 muM, neither induce currents nor block the response to S1P. HEK-293 and COS-1 cells respond with intracellular Ca2+ release to both 50 muM S1P and 10 muM 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.