A search for a model tissue for studying effects of thiazide diuretics

Abstract

A search was made for a model tissue of NaCl absorption which would be sensitive to inhibition by diuretics of the thiazide type. A lack of such a model through the years has hampered the analysis of the cellular mechanism of action of this important class of drugs. Using the short-circuit current technique, the urinary bladders of the toads Bufo spinosus and Bufo marinus, and the frog Rana temporaria were investigated regarding the effects of various thiazides. These bladders have NaCl absorptive properties similar to those of the distal renal tubules, and are claimed to be sensitive to the inhibitory effect of thiazides on sodium transport. The short-circuit current (SCC), which is representative of the sodium transport across the epithelium, was reduced by cyclopenthiazide and polythiazide, but only at high concentrations (above 0.1 mM). To rule out the possibility that this was an unspecific effect, attempts were made to block the effect by the 'thiazide blocker' Ex 4877, but without success. This finding, together with the fact that dose-response curves were difficult to obtain, would indicate that these epithelia are not suitable for the stated purpose. Preliminary studies were also conducted on the urinary bladder of the plaice, Pleuronectes platessa, which has a different system of NaCl absorption that is claimed to be rapidly and reversibly inhibited by thiazides. Polythiazide, added to both sides of the bladder, had no effect on SCC.