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Inhibition by fenamates of calcium influx and proliferation of human lymphocytes
Author(s) -
Kankaanranta H.,
Luomala M.,
Kosonen O.,
Moilanen E.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15698.x
Subject(s) - chemistry , calcium , calcium in biology , flufenamic acid , phorbol , thapsigargin , pharmacology , biochemistry , endocrinology , medicine , receptor , intracellular , protein kinase c , biology , enzyme , organic chemistry
1 Flufenamic and tolfenamic acids have recently been shown to inhibit receptor‐mediated calcium influx in human neutrophils. The present work was designed to study the effects of these two nonsteroidal anti‐inflammatory drugs on human peripheral blood lymphocyte activation. 2 Peripheral blood mononuclear cells (PBMNCs; containing 90% lymphocytes) were stimulated by mitogen concanavalin A (Con A) or by a combination of an inhibitor of microsomal Ca 2+ ‐adenosine triphosphatase thapsigargin (TG) and phorbol myristate acetate (PMA). The effects of the two fenamates on cell proliferation were compared with respective changes in calcium metabolism. 3 Flufenamic and tolfenamic acids (10–100 μ m ) inhibited both Con A and TG+PMA‐induced [ 3 H]‐thymidine incorporation in a dose‐dependent manner. At the same concentration range, the two fenamates inhibited the increase in intracellular free calcium concentration induced by Con A or TG+PMA. This effect was due to inhibition of calcium influx whereas calcium release from intracellular stores remained unaltered. 4 The inhibition of divalent cation influx was confirmed by showing that fenamates inhibited TG+PMA‐induced Mn 2+ influx. 5 The inhibitory effects of fenamates on PBMNC proliferation and Ca 2+ influx were qualitatively similar with those of SK&F 96365, an earlier known inhibitor of receptor‐mediated calcium entry. Ketoprofen, a chemically different prostaglandin synthetase inhibitor did not show similar suppressive effects on PBMNCs. 6 The data suggest that flufenamic and tolfenamic acids suppress proliferation of human peripheral blood lymphocytes by a mechanism which involves inhibition of Ca 2+ influx and is not related to inhibition of prostanoid synthesis.