Inhibition of active chloride transport by piretanide

Abstract

THE mechanism of chloride transport in epithelia is still obscure, although it is the dominant process in many tissues, including the loop of Henle^1,2, cornea³, gastric mucosa⁴, marine teleost gill⁵ and anterior intestine⁶. In contrast with studies on sodium movements, where ouabain has been a potent tool for defining the role of the sodium pump, the site of action of inhibitors of chloride transport (for example, thiocyanate, carbonic anhydrase inhibitors and the diuretics furosemide and bumetanide^6–9) remains undefined. We present here data for piretanide¹⁰ (Fig. 1), a new potent inhibitor of chloride transport, which demonstrate that at least one major site of action is at the mucosal entry step in teleost intestine. To do this we have measured short circuit current, conductance, bidirectional chloride fluxes, chloride uptake, intracellular potential and chloride activity following treatment with the drug.