Rapid decrease in electrical conductance of mammalian duodenal mucosa in vitro

The effects of HCO 3 − on transepithelial conductance of guinea pig (and, in some experiments, rabbit) duodenum have been investigated using stripped preparations in Ussing-type chambers. Initial conductance amounted to ~27 mS/cm 2 . In the presence of serosal or bilateral HCO 3 − (20 mM), it fell to ~15 mS/cm 2 within 60 min. With mucosal HCO 3 − or HCO 3 − -free solutions, conductance decreased to only ~23 mS/cm 2 . In the absence of HCO 3 − , serosal but not mucosal addition of HCO 3 − prompted a steep conductance drop that was 50% complete within 6 min. These effects were the same in proximal and distal segments, whereas conductance levels in the latter were higher. The effects of HCO 3 − required serosal Na + ; they were partly prevented or reversed by serosal ouabain (3 × 10 −5 M), furosemide (10 −3 M), and other loop diuretics, and indomethacin (10 −5 M). Serosal addition of prostaglandin E 2 (10 −7 M, followed by 10 −6 M) reduced conductance from ~22 to ~17 mS/cm 2 . This effect required serosal HCO 3 − and the presence of indomethacin. 8-Br-cyclic adenosine monophosphate (10 −3 M, serosal side) mimicked the effects of prostaglandin E 2 . Indomethacin and prostaglandin E 2 did not influence the secretory flux of HCO 3 − (~0.5 μmol/cm 2 · h, pH-stat method). Our results assign a critical role to serosal HCO 3 − in the maintenance of a low tissue permeability, dependent on the availability of prostaglandins (cyclic adenosine monophosphate) and involving HCO 3 − access to the cell rather than secretion.