Arvidsson S, Carter K, Yanaka A, Ito S, Silen W
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts.
Am J Physiol. 1990 Oct;259(4 Pt 1):G564-70. doi: 10.1152/ajpgi.1990.259.4.G564.
The effects of intracellular acidosis induced by acidification of the basolateral (nutrient) perfusate on the structure and function of the oxynticopeptic cell were studied in in vitro frog gastric mucosa. Changing the pH of the unbuffered nutrient perfusate (UNB) from 7.2 to 3.5 acidified the oxynticopeptic cell with no change in potential difference (PD) or resistance (R). Intracellular pH (pHi), PD, and R were 7.05 +/- 0.01, 16 +/- 1 mV, 165 +/- 7 omega.cm2 before and 6.44 +/- 0.01, 16 +/- 2 mV, 170 +/- 9 omega.cm2 after nutrient acidification. Acid secretion (H+) increased from 0.86 +/- 0.07 to 1.88 +/- 0.18 mu eq.cm-2.h-1. Addition of forskolin to tissues perfused with nutrient pH (pHn) 3.5 decreased PD to 2 +/- 2 mV and further increased H+ to 3.07 +/- 0.19 mu eq.cm-2.h-1. By light and electron microscopy oxynticopeptic cells perfused with UNB, pHn 3.5, appeared normal. Oxynticopeptic cells in tissues pretreated with omeprazole and then exposed to UNB, pHn 3.5, had extensive morphological damage. On increasing the pH of the nutrient perfusate from 3.5 to 7.2 there was prompt recovery of pHi in untreated and forskolin-stimulated mucosae (pHi 6.87 +/- 0.06 and 6.85 +/- 0.04) but no recovery of pHi in tissues pretreated with omeprazole or cimetidine (pHi 6.26 +/- 0.04 and 6.44 +/- 0.06, n = 6, 30 min after reexposure to UNB, pHn 7.2). We conclude that in a secreting mucosa intracellular acidification of the oxynticopeptic cell to pHi 6.4 is associated with normal morphology, PD, R, and increased H+, and that intracellular acidosis is not de facto deleterious.
在体外青蛙胃黏膜中研究了基底外侧(营养)灌注液酸化诱导的细胞内酸中毒对泌酸-胃蛋白酶细胞结构和功能的影响。将未缓冲的营养灌注液(UNB)的pH从7.2变为3.5会使泌酸-胃蛋白酶细胞酸化,而电位差(PD)或电阻(R)无变化。营养灌注液酸化前细胞内pH(pHi)、PD和R分别为7.05±0.01、16±1 mV、165±7 Ω·cm²,酸化后分别为6.44±0.01、16±2 mV、170±9 Ω·cm²。酸分泌(H⁺)从0.86±0.07增加到1.88±0.18 μeq·cm⁻²·h⁻¹。向pH(pHn)为3.5的营养灌注液灌注的组织中添加福斯高林会使PD降至2±2 mV,并使H⁺进一步增加到3.07±0.19 μeq·cm⁻²·h⁻¹。通过光学和电子显微镜观察,用UNB、pHn 3.5灌注的泌酸-胃蛋白酶细胞看起来正常。用奥美拉唑预处理然后暴露于UNB、pHn 3.5的组织中的泌酸-胃蛋白酶细胞有广泛的形态损伤。将营养灌注液的pH从3.5提高到7.2时,未处理和福斯高林刺激的黏膜中的pHi迅速恢复(pHi分别为6.87±0.06和6.85±0.04),但用奥美拉唑或西咪替丁预处理的组织中的pHi没有恢复(pHi分别为6.26±0.04和6.44±0.06,n = 6,重新暴露于UNB、pHn 7.2后30分钟)。我们得出结论,在分泌性黏膜中,泌酸-胃蛋白酶细胞内酸化至pHi 6.4与正常形态、PD、R以及H⁺增加相关,并且细胞内酸中毒实际上并非有害。