Sphingomyelinase causes endothelium-dependent vasorelaxation through endothelial nitric oxide production without cytosolic Ca(2+) elevation.
Neutral sphingomyelinase (N-SMase) elevated nitric oxide (NO) production without affecting intracellular Ca(2+) concentration ([Ca(2+)](i)) in endothelial cells in situ on aortic valves, and induced prominent endothelium-dependent relaxation of coronary arteries, which was blocked by N(omega)-monomethyl-L-arginine, a NO synthase (NOS) inhibitor. N-SMase induced translocation of endothelial NOS (eNOS) from plasma membrane caveolae to intracellular region, eNOS phosphorylation on serine 1179, and an increase of ceramide level in endothelial cells. Membrane-permeable ceramide (C(8)-ceramide) mimicked the responses to N-SMase. We propose the involvement of N-SMase and ceramide in Ca(2+)-independent eNOS activation and NO production in endothelial cells in situ, linking to endothelium-dependent vasorelaxation.
Mogami
Kimiko
K
Department of Molecular Physiology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Kishi
Hiroko
H
Kobayashi
Sei
S
D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D021941:Caveolae / Q000187:drug effects / Q000502:physiology; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis; D002518:Ceramides / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation
C066099:2,3-N-octanoylsphingosine; D051242:Caveolin 1; D022461:Caveolins; D002518:Ceramides; D009569:Nitric Oxide; C097760:N-palmitoylsphingosine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine; D002118:Calcium