Document Detail


Platelets stimulate expression of endothelin mRNA and endothelin biosynthesis in cultured endothelial cells.
MedLine Citation:
PMID:  1873876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Modulation of the biosynthesis of the vasoconstrictor peptide endothelin was studied in cultured endothelial cells. Immunoreactive endothelin (irET) levels were significantly elevated in conditioned medium from bovine pulmonary artery endothelial (BPAE) or human umbilical vein endothelial cells when coincubated with washed human platelets. Platelets (approximately 200,000 cells/microliters) enhanced irET levels approximately 250% over basal levels. Stimulation of irET levels in BPAE cell-conditioned medium by platelets was time and platelet number dependent. Platelets, as well as thrombin and transforming growth factor-beta 1, stimulated the expression of preproendothelin-1 mRNA in a time-dependent manner. Coincubation of low doses of thrombin (0.1 unit/ml) and subthreshold concentrations of platelets with BPAE cells resulted in a further enhancement of irET levels in conditioned medium. Platelet-mediated stimulation of irET production was not significantly affected by indomethacin (1 microM) or the platelet-activating factor receptor antagonist WEB 2086 (1 microM); however, coincubation of endotoxin (100 ng/ml) with platelets and BPAE cells resulted in significantly higher levels of irET. Whether direct contact or adhesion between platelets and endothelial cells is necessary for stimulating irET release was studied by separating platelets from BPAE cells with a 0.4 microns permeable membrane. Under these conditions, platelets still produced significant elevations (approximately 190% over basal levels) in irET levels in BPAE cell-conditioned medium. In addition, platelet-free buffer from agonist-induced platelet aggregation also significantly enhanced irET production (200% over basal values). These data indicate that a platelet-derived regulatory factor can induce the biosynthesis of endothelin from cultured endothelial cells and also suggest that platelets might play a role in vasomotor regulation via a novel intercellular interaction with the endothelium.
Authors:
E H Ohlstein; B L Storer; J A Butcher; C Debouck; G Feuerstein
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Circulation research     Volume:  69     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-09-26     Completed Date:  1991-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  832-41     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, SmithKline Beecham Research Laboratories, King of Prussia, Pa. 19406-0939.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Platelets / drug effects,  physiology*
Blotting, Northern
Cattle
Cells, Cultured
Culture Media
Endothelins / analysis,  biosynthesis*,  genetics*
Endothelium, Vascular / cytology,  metabolism*
Endotoxins / pharmacology
Humans
Indomethacin / pharmacology
Pulmonary Artery
RNA, Messenger / analysis*
Radioimmunoassay
Thrombin / pharmacology
Umbilical Veins
Chemical
Reg. No./Substance:
0/Culture Media; 0/Endothelins; 0/Endotoxins; 0/RNA, Messenger; 53-86-1/Indomethacin; EC 3.4.21.5/Thrombin

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


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