Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.