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Differential actions of Sphingosine‐1 Phosphate (S1P) receptors in the regulation of microvessel permeability in rat mesenteric venules
Author(s) -
Zhang gengqian,
Wang Qian,
He Pingnian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.950.10
Subject(s) - microvessel , platelet activating factor , sphingosine , sphingosine 1 phosphate , vascular permeability , s1pr1 , evans blue , endothelium , receptor , chemistry , antagonist , medicine , permeability (electromagnetism) , endocrinology , microbiology and biotechnology , biology , angiogenesis , biochemistry , membrane , vascular endothelial growth factor a , vascular endothelial growth factor , vegf receptors
Our previous study demonstrated that preperfusing microvessels with S1P prevented platelet‐activating factor (PAF)‐induced endothelial gap formation and the increases in hydraulic conductivity, Lp. In vitro studies indicated that three different S1P receptors (S1PRs) existed in vascular endothelium, and play different roles in regulating endothelial functions. Our present study aims to identify the S1PRs responsible for the protective effect of S1P on PAF‐stimulated microvessels. Lp was measured in individually perfused rat mesenteric venules. Endothelial gap formation was examined three‐dimensionally with confocal microscopy using fluorescence microspheres (100 nm) as markers. The roles of S1PRs in the S1P effect were investigated using S1PR1 and S1PR3 antagonist, VPC23019 and S1PR2 antagonist, JTE‐013. Neither of the antagonist alone changed baseline Lp. Preperfusing vessels with VPC23019 (10 μM) for 30 min following 20 min perfusion of S1P (1 μM) plus VPC23019 abolished the inhibitory effect of S1P on PAF‐induced endothelial gap formation and the Lp increases. The magnitude of endothelial gap formation and the peak increases in Lp were similar to those obtained in PAF‐stimulated vessels in the absence of S1P. In contrast, preperfusing microvessels with JTE‐013 (10 μM) for 30 min showed no effect on the inhibitory effect of S1P on PAF stimulated vessels. Our results indicated that S1PR1 and/or 3, not S1PR2, are responsible for the protective role of S1P in permeability of intact microvessels by preventing the formation of endothelial gaps. Supported by HL56237 and HL084338.