Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: Pertussis toxin sensitive

Fred L. Minnear, Longkun Zhu, Pingnian He

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Sphingosine 1-phosphate (S1P) is a biologically active lipid. In vitro, S1P tightens the endothelial barrier, as assessed by a rapid increase in electrical resistance and a decrease in solute permeability. We hypothesized that this activity of S1P would also occur in vivo. Hydraulic conductivity (L p), an assessment of endothelial barrier function, was measured in individually perfused venules in rat mesenteries. S1P (1 μM) decreased basal Lp by 63% when basal Lp was between 3.6 and 4.1 × 10-7 cm·s-1·cmH2O-1 but showed no effect when basal LP was below 2 × 10-7 cm·s-1·cmH2O-1. Under either condition, S1P blocked the sixfold increase in Lp induced by platelet-activating factor (PAF, 10 nM). Perfusion of venules with pertussis toxin (0.1 μg/ml), a specific inhibitor of the inhibitory G protein, G i, for 3 h did not affect basal Lp or the increased L p induced by PAF. Pertussis toxin, however, significantly attenuated the inhibitory action of S1P on the PAF-induced increase in Lp, indicating the involvement of the Gi protein. Measurement of endothelial cytoplasmic Ca2+ concentration ([Ca2+] i) in venules loaded with fura-2 AM showed that S1P alone transiently increased basal endothelial [Ca2+]i (from 89 nM to 193 nM) but had no effect on the magnitude and time course of the PAF-induced increase in endothelial [Ca2+]i. These results indicate that S1P functions in vivo to prevent the PAF-induced increase in microvessel permeability. The inhibitory action of S1P involves the pertussis toxin-sensitive Gi protein and is not mediated by prevention of the PAF-induced increase in endothelial [Ca2+]i.

Original languageEnglish (US)
Pages (from-to)H840-H844
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number2 58-2
DOIs
StatePublished - Aug 2005

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: Pertussis toxin sensitive'. Together they form a unique fingerprint.

Cite this