Different effects of cell-permeable ceramide analogs on platelet activation.
The effects of cell-permeable ceramide analogs on platelet responses induced by agonists were investigated. When washed rabbit platelets were pretreated with ceramide and then stimulated with thrombin or U46619, C2-ceramide (N-acetylsphingosine) dose-dependently inhibited the aggregation and arachidonic acid liberation, whereas C6-ceramide (N-hexanoylsphingosine) and C8-ceramide (N-octanoylsphingosine) enhanced these responses. Furthermore, C6-ceramide, but not C2-ceramide, enhanced the increase in and prevented the progressive decrease in cytoplasmic free Ca2+ concentration induced by U46619. On the other hand, treatment with sphingomyelinase potentiated the aggregation in response to U46619. These results indicate that the effects of cell-permeable ceramide analogs on platelet activation vary with N-acyl chain length.
Hashizume
T
T
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Japan.
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 / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
C011439:1,2-diacylglycerol; C066099:2,3-N-octanoylsphingosine; D002518:Ceramides; D004075:Diglycerides; C064769:N-acetylsphingosine; D010975:Platelet Aggregation Inhibitors; C101954:N-caproylsphingosine; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013108:Sphingomyelin Phosphodiesterase; D013917:Thrombin; D013110:Sphingosine; D002118:Calcium