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INTERACTION OF THE NON‐STEROIDAL ANTIINFLAMMATORY DRUG FLUFENAMIC ACID WITH GASTRIC ACID SECRETION AND H + /K + ‐ATPase
Author(s) -
Beil W.,
Greite C.,
Sewing KF.
Publication year - 1992
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1992.tb00504.x
Subject(s) - flufenamic acid , chemistry , parietal cell , gramicidin , mole , atpase , enzyme , vesicle , stimulation , gastric acid , biochemistry , secretion , membrane , biology , endocrinology
SUMMARY 1. The effects of the non‐steroidal anti‐inflammatory drug (NSAID) flufenamic acid on H + production in isolated and enriched guinea‐pig parietal cells and on H + /K + ‐ATPase activity in ion‐tight inside‐out membrane vesicles from pig gastric mucosa were studied. 2. At low concentrations (0.1 and 1.0 μmol/L), flufenamic acid increased the secretory response of parietal cells to dibutyryl cyclic AMP (dbcAMP). At higher concentrations (10 and 100 μmol/L) it progressively inhibited basal and dbcAMP‐stimulated acid production. 3. Flufenamic acid (10 μmol/L) increased K + (0.5–10.0 mmol/L) and K + (0.5–1.0 mmol/L) plus gramicidin‐stimulated ATPase activity in gastric membrane vesicles. The K m value for K + (1.6 and 1.0 mmol/L in the absence and presence of gramicidin, respectively) was decreased to 0.8 and 0.5 mmol/L, respectively. At higher concentrations (≥ 50 μmol/L), flufenamic acid inhibited K + plus gramicidin‐stimulated ATPase activity (inhibited concentration at 50% [IC 50 ] = 186 μmol/L) and reduced the proton concentration (IC 50 = 50 μmol/L). 4. It is concluded that flufenamic acid‐induced enhancement of dibutyryl cyclic AMP‐stimulated H + production in the parietal cell reflects the stimulation of H + /K + ‐ATPase. We suggest that activation of the enzyme involves increased affinity of K + towards the K + ‐binding site of the enzyme and/ or increased KC1 permeability at the vesicle membrane. The inhibitory action of the drug on H + production in parietal cells results from a detergent and/or protonophoric‐like action at the apical parietal cell membrane, and from inhibition of H + /K + ‐ATPase activity.