Intracellular pH in isolated Necturus antral mucosa in simulated ulcerogenic conditions.
Intracellular pH (pHi) was measured with proton-sensitive liquid sensor microelectrodes in isolated Necturus antral mucosa, paying special attention to arranging experimental conditions to simulate conditions frequently associated with in vivo "stress ulceration." Intracellular pH in mucosas perfused under standard conditions (Ringer's solution containing HCO3-/CO2) was 7.22 + 0.02 (n = 27). Removal of Na+ and HCO3- or addition of amiloride or 4-acetamido-4-isothiocyanostillbene-2,2-disulfonic acid (blockers of Na+/H+ and Cl-/HCO3-exchangers) had no influence on steady-state pHi, suggesting that these ion exchangers do not significantly contribute to the maintenance of pHi in the presence of normal external pH. Acidification of mucosal (luminal) perfusate to pH 3 (mimicking the presence of gastric acid) had no influence on pHi, but mucosal pH 2 (10 mM HCl) acidified pHi to 6.93 +/- 0.07. Acidification of serosal (nutrient) perfusate to pH 6 (mimicking intramucosal acidosis caused by back-diffusion of luminal H+) acidified pHi to 6.72 +/- 0.10. Removal of Na+ from and addition of amiloride to the serosal perfusate during exposure to serosal pH 6.0 induced further acidification of pHi, suggesting that in this acidotic situation (with very low ambient HCO3- concentration) a Na+/H+ exchanger does contribute to the maintenance of steady-state pHi. Increased PCO2 (10% vol/vol in the gas) in a slightly acidic milieu (mimicking mucosal ischemia) likewise acidified pHi to 6.73 +/- 0.05. A combination of mucosal acid (pH 3), high PCO2 (10% CO2), and low serosal pH (pH 6) (mimicking conditions that prevail, for example, during hemorrhagic shock) acidified pHi and ultimately resulted in cell death. These derangements of intracellular acid-base balance may have pathogenetic importance also in in vivo stress ulceration.
Kivilaakso
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E
Second Department of Surgery, Helsinki University Central Hospital, Finland.
Kiviluoto
T
T
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002254:Carbonates / Q000502:physiology; D005753:Gastric Mucosa / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D007552:Isotonic Solutions / Q000494:pharmacology; D008564:Membrane Potentials; D008839:Microelectrodes; D009337:Necturus; D011706:Pyloric Antrum / Q000502:physiology; D000077331:Ringer's Solution; D012964:Sodium / Q000502:physiology; D013276:Stomach Ulcer / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology
D002254:Carbonates; D007552:Isotonic Solutions; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C005686:sodium carbonate; D000584:Amiloride; D000077331:Ringer's Solution; D012964:Sodium