Document Detail

Flufenamic and tolfenamic acids inhibit calcium influx in human polymorphonuclear leukocytes.
MedLine Citation:
PMID:  7746266     Owner:  NLM     Status:  MEDLINE    
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.
H Kankaanranta; E Moilanen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmacology     Volume:  47     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-06-12     Completed Date:  1995-06-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1006-13     Citation Subset:  IM    
Medical School, University of Tampere, Finland.
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MeSH Terms
Anthranilic Acids / pharmacology*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Calcimycin / pharmacology
Calcium / metabolism*
Calcium Channel Blockers / pharmacology
Diphenylamine / analogs & derivatives,  pharmacology
Flufenamic Acid / pharmacology*
Imidazoles / pharmacology
Intracellular Fluid / metabolism
Ion Transport / drug effects
Ketoprofen / pharmacology
Manganese / metabolism
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Neutrophils / drug effects*,  metabolism*
Nifedipine / pharmacology
Reg. No./Substance:
0/Anthranilic Acids; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Calcium Channel Blockers; 0/Imidazoles; 122-39-4/Diphenylamine; 130495-35-1/1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; 13710-19-5/tolfenamic acid; 17870-85-8/3',5-dichlorodiphenylamine-2-carboxylic acid; 21829-25-4/Nifedipine; 22071-15-4/Ketoprofen; 52665-69-7/Calcimycin; 530-78-9/Flufenamic Acid; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 7439-96-5/Manganese; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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