Sphingosine enhances arachidonic acid liberation in response to U46619 through an increase in phospholipase A2 activity in rabbit platelets.
Treatment of rabbit platelets for 1 min with 10-15 microM sphingosine enhanced arachidonic acid liberation after stimulation with U46619, although sphingosine or U46619 alone elicited little liberation of the lipid. Thrombin-induced arachidonic acid liberation was not influenced by sphingosine up to 10 microM, and was suppressed at concentrations higher than 20 microM. Sphingosine also promoted lysophosphatidylcholine formation in response to U46619, indicating that sphingosine caused an increase in hydrolytic action of phospholipase A2 (PLA2). The enhancing effect of sphingosine on arachidonic acid liberation decreased with increases in pretreatment time, accompanied by the conversion of sphingosine to sphingosine-1-phosphate. Of various sphingosine derivatives examined, sphingosine-1-phosphate, N,N-dimethylsphingosine, and N-acetylsphingosine (C2-ceramide) showed little enhancing effect on arachidonic acid liberation. Sphingosine increased cytosolic PLA2 activity in response to U46619 with enhancement of mitogen-activated protein kinase activity. These results indicate that sphingosine potentiates the transduction process of stimulus-PLA2 activation, resulting in enhancement of arachidonic acid liberation.
Hashizume
T
T
Department of Pathological Biochemistry, Kyoto Pharmaceutical University.
Nakao
M
M
Kageura
T
T
Sato
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood*; D001711:Biotransformation; D001792:Blood Platelets / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D013110:Sphingosine