Model of bicarbonate secretion by resting frog stomach fundus mucosa I. Transepithelial measurements

Abstract

In the present in vitro experiments on gastric fundus mucosa of Rana esculenta we try to define the mechanism of alkaline secretion that is observed in summer frogs in the resting stomach (blockage of HCl secretion by ranitidine, 10⁻⁵ mol/l). The transepithelial voltage and the rate of alkalinization (ASR) of an unbuffered gastric lumen perfusate was measured as a function of serosal (and mucosal) fluid composition. ASR was high (0.88±S.E. 0.09 μEq·cm⁻²·h⁻¹, n=11) during serosal bath perfusion with HCO₃ ⁻-Ringer solution, decreased slightly to 0.50±0.07 μEq·cm⁻²·h⁻¹ (n=6) in HCO₃ ⁻-free HEPES-buffered Ringer solution of the same pH, and decreased to approximately 20% when carbonic anhydrase was inhibited by acetazolamide. While replacement of mucosal or serosal Cl⁻ did not — within 1 h — significantly alter ASR, replacement of serosal Na⁺ in the presence or absence of HCO₃ ⁻ strongly reduced ASR, and a similar reduction was observed after serosal application of the anion transport inhibitor DIDS (4,4-diisomiocyanatostilbene-2,2-disulphonate, 2·10⁻⁴ mol/l), the metabolic poison rotenone (10⁻⁵ mol/l), the uncoupler dinitrophenol (10⁻⁴ mol/l), and the Na⁺ pump inhibitor ouabain (10⁻⁴ mol/l), while serosal amiloride (10⁻⁴ mol/l) had no effect. These data can be accounted for by a model of alkaline secretion that consists of basolateral HCO₃ ⁻ uptake from the serosal fluid into the cell via a DIDS-inhibitable Na⁺(HCO₃ ⁻)_n-cotransporter and HCO₃ ⁻ secretion from the cell to the gastric lumen via an anionic conductance pathway. Microelectrode experiments on oxyntopeptic cells reported in the subsequent paper suggest that these cells may also be involved in the resting state alkaline secretion.