[Effects of sphingosine-1-phosphate, a lipid mediator, in cardiovascular tissues]

Effects of sphingosine-1-phosphate (S1P), a putative lipid mediator, was examined in vascular smooth muscle and endothelial cells by means of measuring intracellular Ca2+ concentration ([Ca2+]i), whole-cell membrane currents and tension. Application of S1P in a concentration range from 30 to 1000 nM to human umbilical vein endothelial cells (HUVECs) induced a slowly developing increase in [Ca2+]i. and concomitant non-selelctive cationic inward currents. Pretreatment of HUVECs with pertussis toxin (PTX) almost abolished the S1P-induced elevation of [Ca2+]i, suggesting that PTX sensitive edg1 receptors are involved in the S1P-induced response in HUVECs. Moreover, treatment of HUVECs with S1P for 24 hrs caused cell-proliferation to 150% of the control. On the other hand, application of S1P had no effect on [Ca2+]i in rabbit, rat and mouse aortic myocytes. When S1P applied to rabbit aorta with endothelium, the muscle ring had small relaxation which disappeared in endothelium-denuded aorta. In contrast, rat cerebral arterial myocytes had increase in [Ca2+]i in the presence of S1P. These results suggest that responses of vascular tissues to S1P vary from cell to cell. To clarify physiological and pharmacological significance of S1P in cardiovascular system, comprehensive analyses are required.