Hydroxylated 22-carbon fatty acids in platelet and vascular smooth muscle function: interference with TXA2/PGH2 receptors.
Sub-micromolar levels of the lipoxygenase products of n-3 fatty acids specifically antagonize both the contractile effects of thromboxane (U46619) and its platelet aggregating effect. In addition, OH-22:6n3 inhibits thromboxane-induced decreases in cerebral blood flow of the rat. Analysis of binding parameters indicates these derivatives induce a marked decrease in the affinity of the TXA2/PGH2 receptor for thromboxane with a mild change in the number of receptor sites. The 22-carbon n-3 hydroxy fatty acids are the most potent biological antagonists of thromboxane in comparison to the n-6 hydroxy fatty acids and their parent fatty acids. Dietary permutations modify the hydroxy fatty acid profile and correlate with changes in thromboxane-mediated responses.
Karanian
J W
JW
Laboratory of Membrane Biochemistry and Biophysics, DICBR, NIAAA, Bethesda, MD 20892.
Salem
N
N
D000818:Animals; D001681:Biological Assay; D001792:Blood Platelets / Q000378:metabolism*; D004032:Diet; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2
D005231:Fatty Acids, Unsaturated; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2