TY - JOUR T1 - Flufenamic and tolfenamic acids inhibit calcium influx in human polymorphonuclear leukocytes. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1006 LP - 1013 VL - 47 IS - 5 AU - H Kankaanranta AU - E Moilanen Y1 - 1995/05/01 UR - http://molpharm.aspetjournals.org/content/47/5/1006.abstract N2 - Fenamates, a subgroup of nonsteroidal anti-inflammatory drugs, inhibit several functions of human polymorphonuclear leukocytes (PMNs) in vitro, by a thus far unknown mechanism. To determine the mechanism behind this action, we studied the effects of two fenamates (flufenamic and tolfenamic acids) on Ca2+ metabolism in human PMNs. The two fenamates inhibited the increases in intracellular free calcium concentration induced by either the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine or the calcium ionophore A23187 in fura-2-labeled PMNs. This inhibition was concluded to be due to blocking of the cation influx, as evidenced by measurement of Mn2+ influx and the influx of radioactive calcium. In addition, the actions of flufenamic and tolfenamic acids were similar to those of an experimental blocker of nonselective cation channels (SK&F 96365). The two other control compounds, an antagonist of voltage-dependent calcium channels (nifedipine) and an inhibitor of prostanoid synthesis (ketoprofen), were ineffective. In conclusion, inhibition of calcium influx in PMNs is introduced as a novel prostanoid-independent mode of action of two nonsteroidal anti-inflammatory drugs with fenamate structure, flufenamic and tolfenamic acids, which could explain their earlier documented inhibitory effects on PMN functions. ER -