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Biomedical subjects

M S Minkes

Publications and source records attributed to M S Minkes.

7 recordsLinked to original sources
PubMed1979

Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties.

Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1977

Characterization of a novel metabolic pathway of arachidonate in coronary arteries which generates a potent endogenous coronary vasodilator.

Bovine coronary artery strips were incubated with [1-14C]arachidonic acid and the chemical properties of the various prostaglandins (PG) formed were studied. Arachidonate was converted to two major prostaglandin products, PGE2 and a novel prostaglandin having chemical (i.e. base hydrolysis and borohydride reduction) and chromatographic properties identical with 6-keto-PGF1alpha. This final compound was inactive on coronary artery strips. The endoperoxide intermediates, PGG2 or PGH2, previously shown to induce coronary relaxation, were not released into the medium from isolated bovine coronaries. The arachidonic acid-induced dilation may have been due to an intracellular action of PGH2 (or PGG2) or to the action of another, yet unidentified, labile intermediate formed in the enzymatic conversion of endoperoxides to 6-keto PGF1alpha. When PGH2 was incubated with bovine coronary microsomes, the PGH2 was completely metabolized (i.e. loss of rabbit aorta contraction) but a compound was generated which was a much more potent coronary relaxant. We suggest that this major novel metabolic pathway of arachidonate generates a substance, intermediate between PGH2 and the final 6-keto PGF1alpha-like product, which is a potent coronary vasodilator.

Animals↗