Vessel-specific role of sphingosine kinase 1 in the vasoconstriction of isolated basilar arteries.
Vessel-specific role of sphingosine kinase 1 in the vasoconstriction of isolated basilar arteries.
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DOI:
10.1016/j.phrs.2010.09.002
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发表时间:
2010-12
影响因子:
9.3
通讯作者:
Waeber, Christian
中科院分区:
文献类型:
--
作者:
Salomone, Salvatore;Soydan, Guray;Ip, Peter Ching-Tze;Hopson, Kristen M. Park;Waeber, Christian
Sphingosine-1-phosphate (S1P) constricts cerebral arteries through S1P3 receptor stimulation. Because the activity of the key S1P-synthesizing enzyme, sphingosine kinase (SPK), can be stimulated by agonists of various G protein-coupled receptors, it is likely that S1P also acts as a second messenger for other vasoconstrictors. We investigated the effect of SPK inhibitors and SPK gene deletion on the contractile responses of isolated vessels to vasoactive agonists and KCl-induced depolarization. Basilar and femoral arteries of rat, mounted in a wire myograph, were incubated with dimethylsphingosine (DMS), 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (Compound 2) or FTY720, and exposed to KCl, 5-hydroxytryptamine (5-HT), S1P or phenylephrine (PE). Vasomotor responses in basilar artery were decreased by DMS, Compound 2 and FTY720, while they were not affected in femoral artery. Basilar artery from SPK1−/− mice exhibited weaker vasoconstriction to both KCl and agonists (S1P and the prostanoid U46619) when compared to either wild type (WT) or SPK2−/−. In contrast, in mesenteric resistance arteries, neither the contraction to KCl nor the maximum contraction to PE and S1P significantly differed among WT, SPK1−/− and SPK2−/−. Quantitative analysis of SPK mRNA (reverse transcription and real time polymerase chain reaction) in mouse arteries showed 40–80-fold higher SPK1 expression in cerebral arteries than in aorta or mesenteric arteries. SPK1 critically modulates the reactivity of cerebral vasculature to vasoconstrictors. S1P plays a specific role as modulator of cerebral blood flow, potentially acting either directly outside vascular smooth muscle cells on S1P3 receptors, or indirectly after being generated inside the cell in response to vasoconstrictors.
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DOI:
10.1016/j.bbalip.2009.02.011
发表时间:
2009-07
期刊:
Biochimica et biophysica acta
影响因子:
--
作者:
Kim RH;Takabe K;Milstien S;Spiegel S
通讯作者:
Spiegel S
影响因子:
20.1
作者:
Peter, Bernhard Friedrich;Lidington, Darcy;Bolz, Steffen-Sebastian
通讯作者:
Bolz, Steffen-Sebastian
影响因子:
7.3
作者:
Salomone, S.;Potts, E. M.;Waeber, C.
通讯作者:
Waeber, C.
影响因子:
37.8
作者:
Bolz, SS;Vogel, L;Pohl, U
通讯作者:
Pohl, U
影响因子:
20.1
作者:
MULVANY, MJ;HALPERN, W
通讯作者:
HALPERN, W