Dietary fat modifies thromboxane A2-induced stimulation of rat platelets.
Diets containing high levels of monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids were fed to Wistar rats. This resulted in decreases in the arachidonate content in platelet phospholipids to 91%, 79% and 51% respectively of the level found after feeding a diet rich in saturated fatty acids. In the presence of CaCl2, collagen- and thrombin-induced aggregation of washed platelets from the saturated-fat dietary group (with highest level of arachidonate) was low compared with that of platelets from the other dietary groups, despite a relatively high production of thromboxane B2. On the other hand, n-3 polyunsaturated fatty acids in the diet resulted in platelets aggregating actively, but producing low levels of levels of thromboxane B2. When indomethacin-treated rat platelets were activated with the thromboxane A2 analogue U46619, the presence of a second agonist such as collagen. ADP or thrombin was necessary for aggregate formation. U46619-induced aggregation in combination with either co-activator was relatively low in arachidonate-rich platelets, and was higher in platelets with a low arachidonate content. Similarly, phospholipase C-catalysed formation of L-myo-inositol phosphates was higher in platelets with a low arachidonate content. We conclude that the ability of platelets to react with thromboxane A2 is modified by diet in such a way that a decreased substrate-limited generation of thromboxane A2 is compensated for by an increased response to thromboxane, and vice versa. No significant differences were detected in the binding of U46619 or SQ29548 to platelets from the various dietary groups. Therefore the changed response seems not to be caused by modified properties of the thromboxane A2/prostaglandin H2 receptors, but by altered transduction of the thromboxane signal.
Heemskerk
J W
JW
Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
Feijge
M A
MA
Kester
A
A
Hornstra
G
G
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D003094:Collagen / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D008297:Male; D015539:Platelet Activation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D004041:Dietary Fats; D011450:Prostaglandin Endoperoxides, Synthetic; D007294:Inositol; D013928:Thromboxane A2; D003094:Collagen; D010738:Type C Phospholipases; D013917:Thrombin; D002118:Calcium; D007213:Indomethacin