Inhibition of chloride/bicarbonate antiports in monkey kidney cells (Vero) by non-steroidal anti-inflammatory drugs.
Two chloride/bicarbonate antiport mechanisms are involved in the regulation of cytosolic pH (pHi) in Vero cells, namely Na+-dependent chloride/bicarbonate antiport to normalize pHi after acidification of the cytosol, and Na+-independent Cl-/HCO3- exchange to regulate pHi back to normal after alkalinization of the cytosol. We have tested the effects of the non-steroidal anti-inflammatory drugs acetylsalicylic acid (aspirin), salicylic acid, indomethacin and piroxicam on chloride/bicarbonate exchange and on chloride self exchange in Vero cells. All these drugs were found to inhibit both the Na+-independent and the Na+-linked chloride/bicarbonate antiport in a dose dependent manner. The Na+-independent chloride/bicarbonate antiport was inhibited by lower doses of the drugs than the Na+-linked antiport. The ability of the drugs to inhibit chloride self exchange did not vary much with varying external pH, indicating that the inhibitory effect is due to the anionic form of the drugs. Inhibition occurred immediately upon addition of the drugs, and it was rapidly reversible, indicating that the inhibitory effect is due to direct interaction of the drugs with chloride/bicarbonate antiport, and not to inhibition of prostaglandin synthesis. The relevance of our findings to the clinical effects of the drugs is discussed.
Tønnessen
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TI
Department of Biochemistry, Norwegian Radium Hospital, Montebello, Oslo.
Aas
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Sandvig
K
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Olsnes
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D012964:Sodium / Q000378:metabolism; D014709:Vero Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D002712:Chlorides; D012459:Salicylates; D012964:Sodium; D020156:Salicylic Acid