Document Detail


Inhibitory mechanism of cis-polyunsaturated fatty acids on platelet aggregation: the relation with their effects on Ca2+ mobilization, cyclic AMP levels and membrane fluidity.
MedLine Citation:
PMID:  2166588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The in vitro inhibitory effects of cis-polyunsaturated fatty acids, linolenic (18:2 delta 9,12), alpha-linoleic (18:3 delta 9,12,15) and eicosatrienoic (20:3 delta 11,14,17) acid, on bovine platelet aggregation and their inhibitory mechanism were investigated. These fatty acids inhibited platelet aggregation induced by ADP and thrombin to similar extent. Fluorescence analyses with fura-2-loaded platelets showed that, in the concentration ranges that inhibited aggregation, they also inhibited agonist-induced increase in cytoplasmic Ca2+. According to radioimmunoassay study, addition of these fatty acids increased cyclic AMP contents in the presence of theophylline corresponded with their inhibitory effects on aggregation. These fatty acids induced a 1.6-1.8-fold increase over basal concentration of cyclic AMP in the concentration ranges that fully inhibited aggregation. On the other hand, saturated fatty acid, stearic acid, affected neither aggregation nor cyclic AMP levels. As reported previously [1985) Biochim. Biophys. Acta 818, 391), these unsaturated fatty acids induced increase in membrane fluidity in the same concentration range. These results suggest that inhibition of platelet aggregation by cis-polyunsaturated fatty acids is due to the increase in cyclic AMP levels. This increase seems to be due to stimulation of adenylate cyclase which is mediated by membrane perturbation.
Authors:
S Kitagawa; K Kotani; F Kametani
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1054     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-09-18     Completed Date:  1990-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  114-8     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / pharmacology
Adenylate Cyclase / metabolism
Animals
Calcium / metabolism*
Cattle
Cells, Cultured / drug effects
Cyclic AMP / metabolism*
Cytoplasm / metabolism
Dose-Response Relationship, Drug
Fatty Acids, Unsaturated / pharmacology*
Fluorescence Polarization
Linoleic Acid
Linoleic Acids / pharmacology
Linolenic Acids / pharmacology
Membrane Fluidity / drug effects*
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors*
Stearic Acids / pharmacology
Stereoisomerism
Chemical
Reg. No./Substance:
0/Fatty Acids, Unsaturated; 0/Linoleic Acids; 0/Linolenic Acids; 0/Platelet Aggregation Inhibitors; 0/Stearic Acids; 2197-37-7/Linoleic Acid; 57-11-4/stearic acid; 60-92-4/Cyclic AMP; 7324-41-6/8,11,14-Eicosatrienoic Acid; 7440-70-2/Calcium; EC 4.6.1.1/Adenylate Cyclase

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


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