title: Thiazide diuretics inhibit chloride absorption by rabbit distal colon.
abstract: 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.
mesh_terms: D000818:Animals; D001581:Benzothiadiazines; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003864:Depression, Chemical; D004232:Diuretics; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001581:Benzothiadiazines; D001639:Bicarbonates; D002712:Chlorides; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D012964:Sodium