Ceramide-induced vasorelaxation: An inhibitory action on protein kinase C.
Experiments were designed to examine the role of sphingosine, PP2A phosphatases, and protein kinase C (PKC) inhibition in mediating the vasodilatory effects of ceramide in rat thoracic aorta. Sphingosine did not cause vasorelaxation, and oleoylethanol-amine, a ceramidase inhibitor, did not affect sphingomyelinase-induced relaxation. Okadaic acid potentiated the relaxation response to ceramide. These observations rule out involvement of sphingosine and PP2A phosphatases in mediating ceramide-induced relaxation. Sphingomyelinase attenuated contractile and single-cell intracellular calcium responses to phorbol ester. Chelerythrine incubation potentiated the relaxation response to ceramide. These observations support a role for PKC inhibition in mediating the vasodilatory effects of ceramide.
Johns
D G
DG
Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA. dgjohns@umich.edu
Jin
J S
JS
Wilde
D W
DW
Webb
R C
RC
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D055572:Ceramidases; D002518:Ceramides / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D002518:Ceramides; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D010704:Phorbols; D019319:Okadaic Acid; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D013108:Sphingomyelin Phosphodiesterase; D000581:Amidohydrolases; D055572:Ceramidases; D013110:Sphingosine