The relationship between thromboxane and cytosolic calcium modifiers in rat platelets.
Platelet activity is controlled, in part, by cytosolic free ionized calcium concentration ([Ca++]i). Regulation of platelet thromboxane (TXB2) synthesis may be by regulation of [Ca++]i. Dietary linoleate is a regulator of TXB2 synthesis, therefore, it may act by influencing [Ca++]i. Aspirin is a regulator of TXB2 synthesis by inhibition of cyclooxygenase; ouabain and nifedipine are regulators of [Ca++]i. This study was conducted to determine whether these affectors of TXB2 synthesis and [Ca++]i cause associated responses. Male nonobese Zucker rats were fed diets supplying 30% of energy (en%) as fat. Dietary fat was a mixture of corn oil and beef tallow to provide 3.0, 4.5, 6.0, or 7.5 en% linoleic acid, with cholesterol added to provide equal cholesterol in all diets. Rats were fed for 30 days with 6 rats/diet. Isolated rat platelets were assayed for FA composition; the percentage of linoleic acid in platelet FA rose linearly with increasing dietary linoleate (r = 0.76, P less than 0.0001). Resting and thrombin-stimulated platelet [Ca++]i and TXB2 synthesis were measured in the presence or absence of extracellular calcium and aspirin, ouabain, or nifedipine. Aspirin caused reductions in both parameters; nifedipine blocked [Ca++]i, but did not affect TXB2; ouabain increased both. Changes induced by those modifiers of TXB2 and platelet [Ca++]i caused changes that were in the same direction for both. CaCl2 caused an increase in both and the [Ca++]i was correlated with the square root of the TXB2; without CaCl2 the two were negatively correlated; aspirin, ouabain, and nifedipine treatments resulted in no significant correlations. The results suggest that there is a common modifier of [Ca++]i and TXB2 synthesis.
Krumhardt
B
B
Iowa State University, Department of Food and Nutrition, Ames 50011.
Dupont
J
J
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*
D004041:Dietary Fats; D005227:Fatty Acids; D008041:Linoleic Acids; D013929:Thromboxane B2; D010042:Ouabain; D003094:Collagen; D019787:Linoleic Acid; D013917:Thrombin; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D002122:Calcium Chloride; D001241:Aspirin; D002118:Calcium