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Ionophores stimulate prostaglandin and thromboxane biosynthesis.
Knapp HR, Oelz O, Roberts LJ, Sweetman BJ, Oates JA, Reed PW
(1977) Proc Natl Acad Sci U S A 74: 4251-5
MeSH Terms: Arachidonic Acids, Blood Platelets, Humans, In Vitro Techniques, Ionophores, Kidney Medulla, Male, Prostaglandins, Stimulation, Chemical, Thromboxane B2, Thromboxanes, Time Factors
Show Abstract · Added December 10, 2013
The role of calcium in triggering prostaglandin and thromboxane synthesis was studied in several systems with ionophores of different ion specificities. Divalent cationophore A23187 stimulates prostaglandin and thromboxane production by washed human platelets in a concentration-dependent manner (0.3-9 muM). A23187 also induces an antimycin A-insensitive burst in oxygen utilization which is partially blocked by 5 mM aspirin or 10 muM indomethacin. Under our conditions, A23187 (up to 10 muM) does not appear to damage platelet membranes since it does not cause appreciable loss of lactate dehydrogenase or beta-glucuronidase. 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. 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. X537A, monensin A, and nigericin (all 5 muM) stimulate both prostaglandin output and K(+) efflux from renal medulla, while 5 muM valinomycin or A204 has no effect on either. None of the ionophores stimulates renomedullary prostaglandin production if calcium is omitted from the incubation medium. A23187 also stimulates prostaglandin production by human lymphoma cells, rat stomach and trachea preparations, and guinea pig polymorphonuclear leukocytes. 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.
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12 MeSH Terms
Effects of indomethacin on cyclic nucleotide levels and histamine release from rat serosal mast cells.
Lewis RA, Holgate ST, Roberts LJ, Maguire JF, Oates JA, Austen KF
(1979) J Immunol 123: 1663-8
MeSH Terms: Animals, Arachidonic Acids, Cyclic AMP, Cyclic GMP, Epoprostenol, Histamine Release, Indomethacin, Mast Cells, Prostaglandins D, Rabbits, Rats
Added December 10, 2013
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11 MeSH Terms