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The present work was designed to study the pharmacological control of the receptor-mediated activation of human neutrophils by tolfenamic acid (2(-)[(3-chloro-2-methylphenyl)-amino]benzoic acid). Tolfenamic acid inhibited in a concentration-dependent manner the degranulation response and Ca2+ influx in neutrophils activated either by the chemotactic peptide fMLP (N-formyl-methionyl-leucylphenylalanine) or Ca2+ ionophore A23187 (calcimycin). When fMLP was used to activate neutrophils, tolfenamic acid (30 microM) reduced Ca2+ influx by 50% and degranulation by 20%. A23187-triggered Ca2+ influx and degranulation were inhibited by 60% and 40%, respectively, by 30 microM tolfenamic acid. Tolfenamic acid did not inhibit the release of Ca2+ from intracellular stores induced either by fMLP or A23187. To confirm the inhibition of receptor-mediated cation influx by tolfenamic acid, the agonist induced Mn2+ influx was studied in Ca2+ free medium. Tolfenamic acid (10-30 microM) reduced fMLP-stimulated Mn2+ influx in neutrophils in a concentration-dependent manner. The simultaneous Ca2+ release from intracellular stores was not affected. Protein kinase C activity in sonicated human neutrophils and the purified enzyme from rat brain were inhibited by the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) but not by tolfenamic acid. Both failed to inhibit neutrophil degranulation induced by phorbol myristate acetate, a protein kinase C activator. Tolfenamic acid (100 microM) increased the cellular cAMP levels up to 1.3-fold in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. No effects on cellular cGMP levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
September 1976,
Science (New York, N.Y.),
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
March 1996,
Cellular immunology,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
January 1976,
Scandinavian journal of rheumatology,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
January 1994,
Pharmacology & toxicology,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
January 1999,
Life sciences,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
June 1989,
Clinica chimica acta; international journal of clinical chemistry,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
June 1999,
Immunopharmacology,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
October 2008,
Inflammation research : official journal of the European Histamine Research Society ... [et al.],
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
May 1995,
Molecular pharmacology,
H Kankaanranta, and
H Wuorela, and
E Siltaloppi, and
P Vuorinen, and
H Vapaatalo, and
E Moilanen
December 2017,
Cell reports,
