Inhibition of human neutrophil function by tolfenamic acid involves inhibition of Ca2+ influx
| Autor: | Heikki Vapaatalo, Elise Siltaloppi, Pauli Vuorinen, Eeva Moilanen, Heikki Wuorela, Hannu Kankaanranta |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Neutrophils
Cell Degranulation medicine.drug_class Molecular Sequence Data In Vitro Techniques Pharmacology chemistry.chemical_compound Tolfenamic acid Cyclic AMP medicine Humans ortho-Aminobenzoates Amino Acid Sequence Phosphodiesterase inhibitor Cyclic GMP Calcimycin Protein Kinase C Protein kinase C Glucuronidase Manganese Ionophores Chemistry Degranulation N-Formylmethionine leucyl-phenylalanine Protein kinase inhibitor Calcium Channel Blockers N-Formylmethionine Leucyl-Phenylalanine Biochemistry Depression Chemical Neutrophil degranulation Calcium medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0922-4106 |
| DOI: | 10.1016/0922-4106(95)90184-1 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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