Inhibitory effects of n-6 and n-3 hydroxy fatty acids on thromboxane (U46619)-induced smooth muscle contraction.
Mammalian platelets are capable of enzymatically producing a number of n-6 and n-3 hydroxy fatty acids. Human platelet suspensions produce two major docosahexaenoic acid (22:6n3) metabolites, namely, 11-OH and 14-OH-22:6n3. The hydroxy fatty acids which were formed by human platelets and purified by high performance liquid chromatography specifically antagonize the contractile effects of a thromboxane mimetic, U46619, in airway, visceral and, especially, in the vascular smooth muscle preparations studied. The efficacy of OH-22:6n3 (IC25 = 1.1 microM) was compared to other n-6 and n-3 hydroxy fatty acids in the rat aortic ring preparation. The OH-22:6n3 was significantly more potent with the exception of OH-22:5n3. The rank order of their potency was 14-OH-22:5n3 > or = 14-OH-22:6n3 > 17-OH-22:6n3 > or = 11-OH-22:6n3 > or = 11-OH-22:5n3 > 12-OH-20:5n3 > or = 12-OH-20:4n6 > or = 14-OH-22:5n6 > 13-OH-18:2n6 > 14-OH-22:5n5. Antagonism of thromboxane effects may be an important aspect of the biological function of 22-carbon n-3 hydroxylated fatty acids in platelet-vascular smooth muscle cell interactions.
Karanian
J W
JW
Laboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD.
Kim
H Y
HY
Salem
N
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D004281:Docosahexaenoic Acids; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C059528:14-hydroxydocosahexaenoic acid; C059527:11-hydroxydocosahexaenoic acid