Inhibition of the bicarbonate exit step in urinary acidification by a disulfonic stilbene.
Acidification of the luminal solution by the isolated turtle bladder involves H(+) secretion by a pump at the luminal membrane. The OH(-) dissociated in this process reacts with CO(2) and forms HCO(3) (-) which moves passively out of the cell across the serosal cell membrane. In the present study, this exit step for HCO(3) (-) was inhibited by serosal addition of the disulfonic stilbene, SITS, an agent which is thought to bind to a transport protein at the serosal cell membrane. 90 min after serosal addition of 0.5 mM SITS, H(+) secretion decreased by > 80%. In contrast, luminal addition of SITS had no effect. During inhibition of H(+) secretion by serosal SITS, overall cell pH, measured by the 5, 5-dimethyl-2, 3-oxazolidinedione method, increased from 7.48+/-0.03 to 7.61+/-0.02. This increase of 0.13+/-0.02 pH U was associated with a much larger regional pH increase as judged from the decrement in the attainable pH gradient across the epithelium. After serosal SITS, this gradient was reduced from 2.88+/-0.06 to 2.09+/-0.11 pH U. In the absence of evidence for increased H(+) permeability or a change in the force of the H(+) pump, the gradient decrement of 0.79+/-0.08 U reflects a similar pH increment on the cytoplasmic side of the pump.SITS inhibits the exit of bicarbonate across the serosal cell membrane and, thereby, creates a compartment of high alkalinity in series with the pump. The increased electrochemical gradient across the active transport pathway is the primary factor in the inhibition of urinary acidification.
D000136:Acid-Base Equilibrium; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014426:Turtles; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*
D013267:Stilbenes; D002245:Carbon Dioxide; D010042:Ouabain; D012964:Sodium