SPHINGOSINE ENHANCES ARACHIDONIC-ACID LIBERATION IN RESPONSE TO U46619 THROUGH AN INCREASE IN PHOSPHOLIPASE A(2) ACTIVITY IN RABBIT PLATELETS

Treatment of rabbit platelets for 1 min with 10-15 mu M sphingosine en hanced arachidonic acid liberation after stimulation with U46619, alth ough sphingosine or U46619 alone elicited little liberation of the lip id, Thrombin-induced arachidonic acid liberation was not influenced by sphingosine up to 10 mu M, and was suppressed at concentrations highe r than 20 mu M. Sphingosine also promoted lysophosphatidylcholine form ation in response to U46619, indicating that sphingosine caused an inc rease in hydrolytic action of phospholipase A(2) (PLA(2)), The enhanci ng effect of sphingosine on arachidonic acid liberation decreased with increases in pretreatment time, accompanied by the conversion of sphi ngosine to sphingosine-1-phosphate, Of various sphingosine derivatives examined, sphingosine-l-phosphate, N,N-dimethylsphingosine, and N-ace tylsphingosine (C-2-ceramide) showed little enhancing effect on arachi donic acid liberation, Sphingosine increased cytosolic PLA(2) activity in response to U46619 with enhancement of mitogen-activated protein k inase activity, These results indicate that sphingosine potentiates th e transduction process of stimulus-PLA(2) activation, resulting in enh ancement of arachidonic acid liberation.