Document Detail

Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: pertussis toxin sensitive.
MedLine Citation:
PMID:  15778280     Owner:  NLM     Status:  MEDLINE    
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 (Lp), an assessment of endothelial barrier function, was measured in individually perfused venules in rat mesenteries. S1P (1 microM) decreased basal Lp by 63% when basal Lp was between 3.6 and 4.1 x 10(-7) cm x s(-1) x cmH2O(-1) but showed no effect when basal Lp was below 2 x 10(-7) cm x s(-1) x 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 microg/ml), a specific inhibitor of the inhibitory G protein, Gi, for 3 h did not affect basal Lp or the increased Lp 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.
Fred L Minnear; Longkun Zhu; Pingnian He
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-18
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  289     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-14     Completed Date:  2005-09-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H840-4     Citation Subset:  IM    
Department of Physiology and Pharmacology, PO Box 9229, Robert C. Byrd Health Sciences Center, West Virginia Univ., Morgantown, WV 26506, USA.
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MeSH Terms
Body Water / metabolism*
Capillary Permeability / drug effects*
Lysophospholipids / pharmacology*
Mesentery / blood supply*
Pertussis Toxin / pharmacology*
Platelet Activating Factor / pharmacology*
Rats, Sprague-Dawley
Sphingosine / analogs & derivatives*,  pharmacology
Venules / drug effects,  metabolism
Grant Support
Reg. No./Substance:
0/Lysophospholipids; 0/Platelet Activating Factor; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; EC Toxin

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