Bachmann O, Sonnentag T, Siegel W K, Lamprecht G, Weichert A, Gregor M, Seidler U
Department of Internal Medicine I, University Hospital Schnarrenberg, Eberhard-Karls University Tübingen, D-72076 Tübingen, Germany.
Am J Physiol. 1998 Nov;275(5):G1085-93. doi: 10.1152/ajpgi.1998.275.5.G1085.
Rabbit parietal cells express three Na+/H+ exchanger isoforms (NHE1, NHE2, and NHE4). We investigated the effects of carbachol, histamine, and forskolin on Na+/H+ exchange activity and acid formation in cultured rabbit parietal cells and tested the effect of NHE isoform-specific inhibition on agonist-induced Na+/H+ exchange. Carbachol (10(-4) M) was the weakest acid secretagogue but caused the strongest Na+/H+ exchange activation, which was completely blocked by 1 microM HOE-642 (selective for NHE1); histamine (10(-4) M) and forskolin (10(-5) M) were stronger stimulants of [14C]aminopyrine accumulation but weaker stimulants of Na+/H+ exchange activity. HOE-642 (1 microM) reduced forskolin-stimulated Na+/H+ exchange activity by 35%, and 25 microM HOE-642 (inhibits NHE1 and -2) inhibited an additional 13%, but 500 microM dimethyl amiloride (inhibits NHE1, -2, and -4) caused complete inhibition. The presence of 5% CO2-HCO-3 markedly reduced agonist-stimulated H+ efflux rates, suggesting that the anion exchanger is also activated. Hyperosmolarity also activated Na+/H+ exchange. Our data suggest that, in rabbit parietal cells, Ca2+-dependent stimulation causes a selective activation of NHE1, whereas cAMP-dependent stimulation activates NHE1, NHE2, and more strongly NHE4. Because intracellular pH (pHi) did not change in the presence of CO2-HCO-3 and concomitant activation of Na+/H+ and anion exchange is one of the volume regulatory mechanisms, we speculate that the physiological significance of secretagogue-induced Na+/H+ exchange activation may not be related to pHi but to volume regulation during acid secretion.
兔壁细胞表达三种钠氢交换体亚型（NHE1、NHE2和NHE4）。我们研究了卡巴胆碱、组胺和福斯高林对培养的兔壁细胞钠氢交换活性和酸生成的影响，并测试了NHE亚型特异性抑制对激动剂诱导的钠氢交换的作用。卡巴胆碱（10⁻⁴ M）是最弱的酸分泌剂，但引起最强的钠氢交换激活，1 μM HOE - 642（对NHE1有选择性）可完全阻断；组胺（10⁻⁴ M）和福斯高林（10⁻⁵ M）是[¹⁴C]氨基比林积累更强的刺激剂，但对钠氢交换活性的刺激较弱。HOE - 642（1 μM）使福斯高林刺激的钠氢交换活性降低35%，25 μM HOE - 642（抑制NHE1和 - 2）额外抑制13%，但500 μM二甲基氨氯吡脒（抑制NHE1、 - 2和 - 4）导致完全抑制。5% CO₂ - HCO₃的存在显著降低了激动剂刺激的氢离子外流速率，表明阴离子交换体也被激活。高渗也激活钠氢交换。我们的数据表明，在兔壁细胞中，钙依赖性刺激导致NHE1的选择性激活，而环磷酸腺苷依赖性刺激激活NHE1、NHE2，更强烈地激活NHE4。由于在有CO₂ - HCO₃存在时细胞内pH（pHi）没有变化，并且钠氢和阴离子交换的同时激活是一种容积调节机制，我们推测分泌剂诱导的钠氢交换激活的生理意义可能与pHi无关，而是与酸分泌过程中的容积调节有关。
