Anti-Inflammatory Drugs May Block Bicarbonate Transport
By Biotechdaily staff writers
Posted on 21 Dec 2004
Researchers have found that some carbonic anhydrase inhibitors--including such clinically used anti-inflammatory drugs as celecoxib--will inhibit bicarbonate transport at clinically significant concentrations, which may help to explain the basis for some of the side effects experienced by those taking the drug.Posted on 21 Dec 2004
Investigators at the University of Alberta (Edmonton, Canada; www.ualberta.ca) genetically engineered a variant of the HEK293 cell line to express the human erythrocyte membrane Cl−/HCO3− exchanger, AE1. They then examined the effect of 16 different carbonic anhydrase inhibitors on AE1 transport activity. Among these, 12 were newly reported compounds, two were clinically used nonsteroidal anti-inflammatory drugs (celecoxib and valdecoxib), and two were anticonvulsant drugs (topiramate and zonisamide). The investigators measured transport by following changes of intracellular [Cl−] and pH, using intracellular fluorescent reporter dyes.
Results published in the November 23, 2004, issue of Molecular Membrane Biology revealed that celecoxib and four of the novel compounds significantly inhibited AE1 Cl−/NO3− exchange activity, and that bulkier compounds had greater AE1 inhibitory potency.
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