The ratio of macrophage prostaglandin and leukotriene synthesis is determined by the intracellular free calcium level

Biochemical Pharmacology
V KaeverK Resch

Abstract

The induction of eicosanoid synthesis in various cell types by different physiological stimuli is dependent on an increase in the intracellular calcium level and stimulation of the protein kinase C (PKC). In a model system this can be mimicked by using calcium ionophores and direct PKC activators. In mouse peritoneal macrophages calcium ionophores induced the formation of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4). A synergistic enhancement of both eicosanoids could be achieved by simultaneous addition of the calcium ionophore A23187 together with a suboptimal dose of the direct protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Low concentrations of the ionophore, resulting in only marginally increased intracellular calcium levels, led to a more than additive prostaglandin E2 production in combination with TPA. Higher concentrations of A23187 together with TPA favoured LTC4 synthesis, whereas PGE2 levels at the same time were even diminished. This observed shift from prostaglandin to leukotriene formation was amplified by simultaneous addition of indomethacin. Manganese as inhibitor of the A23187-induced calcium influx decreased PGE2 synthesis. On the other hand, in the presence of manganese LTC4 pro...Continue Reading

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Citations

Dec 24, 1997·Biological Trace Element Research·S O Knowles, W E Donaldson
Jul 1, 1996·Critical Reviews in Oncology/hematology·C Denzlinger
Oct 24, 1998·Prostaglandins & Other Lipid Mediators·T OonishiN Uyesaka
Oct 1, 1993·European Journal of Biochemistry·A Huwiler, J Pfeilschifter
Feb 1, 1992·Prostaglandins, Leukotrienes, and Essential Fatty Acids·D Duval, M Freyss-Beguin
Mar 3, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C R RolandM W Flye

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