Ceramide: a novel cell signaling mechanism for vasodilation.
Ceramide is a lipid second messenger generated by membrane hydrolysis of sphingomyelin by sphingomyelinase, but a role for this novel signaling pathway in vascular smooth muscle has not been elucidated. Based upon observations of cytokine-induced increases in sphingomyelinase activity, we hypothesized that ceramide plays a cell signaling role in vasodilation. Here, we demonstrate that ceramide is present at significant basal levels in cultured vascular smooth muscle cells and that these levels may be increased using exogenous sphingomyelinase. We also report that both exogenously added ceramide and sphingomyelinase cause dose-dependent relaxation in phenylephrine-contracted endothelium-denuded rat thoractic aortic rings. We conclude that the ceramide signaling pathway represents a novel signal transduction mechanism for vasodilation.
Johns
D G
DG
Department of Physiology, University of Michigan, Ann Arbor 48109, USA.
Osborn
H
H
Webb
R C
RC
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D002518:Ceramides; D010656:Phenylephrine; D013108:Sphingomyelin Phosphodiesterase