T1 - Prostaglandin biosynthesis in the human fetal adrenal gland

Prostaglandin and thromboxane production by fibroblasts and vascular endothelial cells.

JO - Prostaglandins Leukotrienes and Medicine

The synthesis of prostaglandins E(2), D(2), and F(2alpha) by rat renal medulla mince is stimulated by 1 and 5 muM A23187 without changes in tissue ATP content, lactate output, or K(+) efflux.

T2 - Prostaglandins Leukotrienes and Medicine

JF - Prostaglandins Leukotrienes and Medicine

AB - 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 (Δ 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.

Comparative aspects of prostaglandin biosynthesis in animal tissues.

AB - The main cyclo-oxygenase-dependent arachidonic acid (AA) derivatives, i.e. prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), have been measured by radioimmunoassay in platelet-free cultures of human monocytes from young and old subjects, in presence and in absence of activating substances (10% fetal calf serum). No difference was found between cells from the two groups as far as the production of PGE2 and TXB2 (stable metabolite of TXA2) was concerned, at variance with reported data in young and old experimental animals. The addition to the cultures of exogenous AA caused a reorientation of cyclic endoperoxide metabolism resulting in a consistent decrease of the ratio TXB2/PGE2, but only in monocytes from young subjects. The data are discussed with respect to the claimed role of prostaglandins in the age-related immune derangement which is present in aged humans.

Biosynthesis of prostaglandins from arachidonic acid in guinea pig lung.


Biosynthesis of prostaglandin D2.

These observations suggest a major role for Ca(2+) in stimulating prostaglandin and thromboxane biosynthesis, and also indicate that prostaglandin and/or thromboxane release may partially mediate some of the previously described effects of ionophores on cells and tissues.

Biosynthesis of prostaglandins and thromboxanes in lung.

AB - The effects of aging on the prostacyclin and thromboxane biosynthesis and prostaglandin catabolic enzyme activity in rat kidney were investigated. The prostacyclin biosynthesis, using arachidonic acid as substrate, was the greatest in young kidneys (2 months old) and then progressively decreased in mature (12 months old) and old (24 months old) kidneys, while thromboxane biosynthetic activity showed no significant change as a function of age. When prostaglandin H2 was used as substrate, the prostacyclin and thromboxane biosynthesis showed similar results as when arachidonic acid was used as substrate; the prostacyclin biosynthesis progressively decreased and thromboxane biosynthesis showed no significant change as a function of age. The fatty acid cyclooxygenase in kidney was measured by a specific radioimmunoassay. No significant change in renal fatty acid cyclooxygenase as a function of age was found. Thus, we concluded that the progressive decrease in renal prostacyclin biosynthesis as a function of age is due to a defect in prostacyclin synthetase in aged kidneys. The prostaglandin catabolic enzyme, NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, in kidneys was also investigated. The enzyme activity progressively decreased as a function of age, which suggested a decrease in the metabolism of thromboxane A2 in aged kidneys. The present results, indicating a decrease in renal prostacyclin biosynthesis and renal 15-hydroxyprostaglandin dehydrogenase activity with aging, might contribute to a plausible explanation of the progressive decrease in renal functions in the elderly.

Drugs which inhibit prostaglandin biosynthesis.

Mono- and divalent cationophore X537A also stimulates platelet thromboxane B(2) production and oxygen utilization, but monovalent cationophores nigericin, monensin A, A204, and valinomycin have no effect.

Pharmacological control of thromboxane A2 in lung.

Mono- and divalent cationophore X537A also stimulates platelet thromboxane B2 production and oxygen utilization, but monovalent cationophores nigericin, monensin A, A204, and valinomycin have no effect.