Document Detail

Attenuation by sphingosine-1-phosphate of rat microvessel acute permeability response to bradykinin is rapidly reversible.
MedLine Citation:
PMID:  22427519     Owner:  NLM     Status:  MEDLINE    
To evaluate the hypothesis that sphingosine-1-phosphate (S1P) and cAMP attenuate increased permeability of individually perfused mesenteric microvessels through a common Rac1-dependent pathway, we measured the attenuation of the peak hydraulic conductivity (L(p)) in response to the inflammatory agent bradykinin (BK) by either S1P or cAMP. We varied the extent of exposure to each agent (test) and measured the ratio L(p)(test)/L(p)(BK alone) for each vessel (anesthetized rats). S1P (1 μM) added at the same time as BK (concurrent, no pretreatment) was as effective to attenuate the response to BK (L(p) ratio: 0.14 ± 0.05; n = 5) as concurrent plus pretreatment with S1P for 30 min (L(p) ratio: 0.26 ± 0.06; n = 11). The same pretreatment with S1P, but with no concurrent S1P, caused no inhibition of the BK response (L(p) ratio 1.07 ± 0.11; n = 8). The rapid on and off action of S1P demonstrated by these results was in contrast to cAMP-dependent changes induced by rolipram and forskolin (RF), which developed more slowly, lasted longer, and resulted in partial inhibition when given either as pretreatment or concurrent with BK. In cultured endothelium, there was no Rac activation or peripheral cortactin localization at 1 min with RF, but cortactin localization and Rac activation were maximal at 1 min with S1P. When S1P was removed, Rac activation returned to control within 2 min. Because of such differing time courses, S1P and cAMP are unlikely to act through fully common effector mechanisms.
R H Adamson; R K Sarai; J F Clark; A Altangerel; T L Thirkill; F E Curry
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-16
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  302     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-16     Completed Date:  2012-07-26     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1929-35     Citation Subset:  IM    
Department of Physiology and Membrane Biology, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
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MeSH Terms
Bradykinin / drug effects,  pharmacology*
Capillary Permeability / drug effects*,  physiology
Cyclic AMP / pharmacology
Forskolin / pharmacology
Lysophospholipids / pharmacology*
Microvessels / drug effects*,  physiology
Models, Animal
Rolipram / pharmacology
Signal Transduction / drug effects,  physiology
Sphingosine / analogs & derivatives*,  pharmacology
Time Factors
Vasodilator Agents / pharmacology*
rac1 GTP-Binding Protein / metabolism
Grant Support
Reg. No./Substance:
0/Lysophospholipids; 0/Vasodilator Agents; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 58-82-2/Bradykinin; 60-92-4/Cyclic AMP; 61413-54-5/Rolipram; 66428-89-5/Forskolin; EC 3.6.1.-/Rac1 protein, rat; EC GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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