Ionophores stimulate prostaglandin and thromboxane biosynthesis.
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.
D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*; D013997:Time Factors
D001095:Arachidonic Acids; D007476:Ionophores; D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2
Prostaglandins. 1977 Apr;13(4):631-47
404671
Biochim Biophys Acta. 1977 Jan 24;496(1):167-74
319839
Prostaglandins. 1977 Feb;13(2):225-34
847230
Biochim Biophys Acta. 1976 Jan 18;486(1):209-13
827311
Proc Natl Acad Sci U S A. 1975 Apr;72(4):1446-50
1055417
Pharmacol Rev. 1974 Mar;26(1):33-67
4208101
Biol Reprod. 1970 Dec;3(3):327-37
4399581
Physiol Rev. 1969 Jan;49(1):122-61
4302663
Biochim Biophys Acta. 1972 Aug 11;270(4):534-45
4403375
Annu Rev Biochem. 1976;45:501-30
786156
J Biol Chem. 1972 Nov 10;247(21):6970-7
4263618
Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400-4
4215079
J Biol Chem. 1975 Dec 25;250(24):9342-7
394
J Biol Chem. 1976 Jun 10;251(11):3489-94
6455
Proc Natl Acad Sci U S A. 1974 Feb;71(2):345-9
4521806
J Gen Physiol. 1975 Nov;66(5):561-81
172596
Acta Med Scand Suppl. 1976;587:71-82
130059
Biochim Biophys Acta. 1968 Oct 1;162(3):320-6
4971376
Prostaglandins. 1975 Dec;10(6):1087-1106
1108118
Nature. 1976 Mar 25;260(5549):337-8
768780
Prostaglandins. 1976 Jan;11(1):3-14
1257497
J Biol Chem. 1976 Apr 25;251(8):2536-8
1262333
Biochim Biophys Acta. 1976 Mar 25;428(1):253-6
1260021
Biochim Biophys Acta. 1975 Apr 18;388(1):71-83
1125304
J Clin Invest. 1975 Apr;55(4):763-70
1120781
Biochim Biophys Acta. 1975 Feb 20;380(2):338-43
1120149
Biochim Biophys Acta. 1968 Oct 22;164(2):430-2
5721038
Biochim Biophys Acta. 1968 Oct 22;164(2):426-9
5721037