Bicarbonate transport, double ion exchange and Na+-Cl- symport are all inhibited by hydrochlorothiazide in the apical membrane of the epithelium of rabbit gallbladder

The transepithelial active transport of fluid in the rabbit gallbladder is related to an apical neutral entry of NaHCO3 and, mainly, NaCl. The latter transfer is due to a bicarbonate-dependent double ion exchange and to a bicarbonate independent Na+ -Cl- symport. Gravimetric measurements of the transepithelial transport show that hydrochlorothiazide inhibits both the bicarbonate dependent and independent fractions, by an inhibition of carbonic anhydrase, a direct action on the symport and perhaps a direct action on the C1-/HCO- 3 exchange. When all the original transports are inactivated by the drug, a new bumetanidesensitive flow of saline is elicited: this is evidence of the activation of a Na+ -K+ -2C1- cotransport. This is the only one known case of a plasma membrane in which all the three forms of neutral coupled transfer of Na+ and Cl- are present together.