Macherey H J, Petersen K U
Institut für Pharmakologie, Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, Wendlingweg, Germany.
Gastroenterology. 1991 Mar;100(3):648-62. doi: 10.1016/0016-5085(91)80008-w.
Electrical conductance as a sensitive indicator of acid damage has been investigated in guinea pig duodenal mucosa using Ussing-chamber techniques. Reductions of luminal pH from 7.4 to 3.0, 2.3, or 2.0 caused concentration-dependent, progressive increases in conductance, accompanied (pH 2.0) by a continuous increase in hydrogen permeation as determined by pH-stat titration. Increases in conductance and hydrogen flux were related to base-line conductance, with higher values conditioning for a sooner onset and/or more marked elevation. Conductance increases were prevented by timely back titration. Recently, it has been shown that serosal HCO3 reduces conductance by actions dependent on prostaglandins and serosal Na and sensitive to loop diuretics. Here, serosal HCO3 delayed the onset of acid-induced conductance increase by approximately 8 minutes, an effect reduced by omission of serosal Na and during exposure to serosal furosemide (10(-3) mol/L). In the presence of serosal indomethacin (10(-4) mol/L) and HCO3, prostaglandin E2 (10(-6) mol/L serosal bath) delayed the conductance increase. Because HCO3 secretion is negligible in this model, these results indicate effects of HCO3/prostaglandin E2 beyond mere buffering of invading hydrogen. These results are consistent with intracellular actions that tighten the paracellular pathway against acid and thus provide temporary protection from acid injury. In agreement with this view, HCO3 also limited conductance increases after luminal alkalinization by a furosemide-sensitive action.
运用尤斯灌流室技术，在豚鼠十二指肠黏膜中研究了电导率作为酸损伤敏感指标的情况。管腔pH从7.4降至3.0、2.3或2.0会导致电导率呈浓度依赖性逐渐增加，在pH为2.0时，通过pH计滴定测定发现氢渗透持续增加。电导率和氢通量的增加与基线电导率相关，基线电导率值越高，酸诱导的电导率增加开始越早且/或升高越明显。及时进行回滴定可防止电导率增加。最近研究表明，浆膜面的HCO₃通过依赖前列腺素和浆膜面Na⁺的作用降低电导率，且对襻利尿剂敏感。在此研究中，浆膜面的HCO₃使酸诱导的电导率增加的起始延迟约8分钟，去除浆膜面Na⁺以及在浆膜面暴露于速尿（10⁻³mol/L）时，这种作用减弱。在浆膜面存在吲哚美辛（10⁻⁴mol/L）和HCO₃的情况下，前列腺素E₂（浆膜浴中10⁻⁶mol/L）也延迟了电导率增加。由于在此模型中HCO₃分泌可忽略不计，这些结果表明HCO₃/前列腺素E₂的作用不仅仅是缓冲侵入的氢离子。这些结果与细胞内作用一致，即细胞内作用收紧细胞旁通道以抵抗酸，从而提供对酸损伤的临时保护。与此观点一致的是，HCO₃在管腔碱化后也通过速尿敏感的作用限制了电导率增加。
