In:
The FASEB Journal, Wiley, Vol. 22, No. S1 ( 2008-03)
Abstract:
In the cardiovascular system, the bioactive lipid sphingosine‐1‐phosphate (S1P) exerts its vasoactive effects predominantly via the S1P 1 , S1P 2 and S1P 3 receptor which are differentially expressed in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs).We have explored the contribution of these three receptors to vascular reactivity in rat aorta and to related signaling mechanisms in isolated VSMCs and ECs using some new S1P receptor ligands. In rat aortic rings, all agonists at the S1P 1 and/or S1P 3 receptor induced endothelium‐dependent vasorelaxation in pre‐contracted preparations. In rat aortic ECs, which showed a high mRNA expression of the G i ‐coupled S1P 1 receptor, all ligands decreased the forskolin‐induced cAMP accumulation whereas no major changes in [Ca 2+ ] i were observed. In VSMCs, which express mRNA for all three S1P receptors, predominantly G q ‐coupled S1P 2 receptor signaling was observed, resulting in increases in [Ca 2+ ] i .In conclusion, the compounds tested in this study can act on both ECs and VSMCs from rat aorta. S1P 1 receptor stimulation in ECs leads to G i activation probably resulting in relaxation via activation of PI3K/Akt and subsequent NO production. Stimulation of mainly the S1P 2 receptor in VSMCs results in calcium elevation, a response typically linked to contraction. For agonists devoid of S1P 2 activity, the net effect observed on aortic tone is thus vasorelaxation.
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fasebj.22.1_supplement.912.4
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1468876-1
detail.hit.zdb_id:
639186-2
SSG:
12
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