[Modulation of sphingosine 1-phosphate, a new lipid mediator, on nitric oxide production by vascular smooth muscle cells].
The effects of sphingosine 1-phosphate (S1P) on nitric oxide (NO) production induced by interleukin (IL)-1 beta in cultured rat vascular smooth muscle cells (VSMCs) have been investigated. Rat VSMCs abundantly expressed mRNA of Edg-3 and Edg-5 receptor subtypes in both unstimulated and IL-1 beta-stimulated cells. S1P at higher than 0.1 microM inhibited the NO production induced by IL-1 beta in a concentration-dependent manner, in which S1P at 10 microM caused over 90% inhibition. S1P also inhibited inducible NO synthase (iNOS) protein and mRNA expressions induced by IL-1 beta in a concentration-dependent manner, which effects were smaller than that in the NO production. S1P also significantly inhibited GTP cyclohydrolase I (GTPCH) mRNA expression induced by IL-1 beta. PTX pretreatment partially prevented the inhibitory effects of S1P on the NO production and iNOS induction, while completely prevented the inhibitory effects on iNOS and GTPCH mRNA expressions. In PTX-pretreated VSMC, S1P showed a bell-shaped enhancing and inhibitory effect on iNOS protein expression. These results suggest that S1P modulates IL-1 beta induction of NO production by rat VSMCs through multiple mechanisms, partially via Edg-3 and Edg-5 receptor subtypes coupled to PTX-sensitive G proteins.
Hirafuji
Masahiko
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan.
Hamaya
Yukihiro
Y
Matsumoto
Yumika
Y
Machida
Takuji
T
Minami
Masaru
M
Kohno
Takayuki
T
Igarashi
Yasuyuki
Y
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology; D008246:Lysophospholipids; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*
D007375:Interleukin-1; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013110:Sphingosine