Thiazide diuretics inhibit chloride absorption by rabbit distal colon

In order to investigate the cellular mechanisms of action of thiazide diuretics, the effect of diuretic and nondiuretic thiazide compounds on Cl- absorption across rabbit distal colon was assessed in tissues mounted in Ussing chambers. This epithelium absorbs Cl- via an active electroneutral transport process. Net 36Cl- absorption across short-circuited tissues was decreased 53, 36 and 20% after addition of 10(-4) M trichlormethiazide, bendroflumethiazide or hydrochlorothiazide, respectively, to the mucosal bathing solution. This inhibitory effect was a result of a decrease in the mucosa-to-serosa unidirectional Cl- flux (P less than .02). Neither the serosa-to-mucosa Cl- flux nor Isc was affected by the thiazides. Thiazide diuretics may exert their effect on Cl- transport across rabbit distal colon through inhibition of a Cl(-)-HCO-3 exchange mechanism. The nondiuretic thiazide, diazoxide, had no effect on Cl- transport. The similarity between the diuretic potency of these compounds and their potency as inhibitors of Cl- absorption by rabbit colon suggests that the thiazides have a similar mechanism of action in renal epithelia.