Maher M M, Gontarek J D, Jimenez R E, Donowitz M, Yeo C J
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Dig Dis Sci. 1996 Apr;41(4):651-9. doi: 10.1007/BF02213119.
Na+/H+ exchanger isoforms have been identified in mammalian intestinal enterocytes and cloned: NHE1 on the basolateral membrane regulating intracellular pH; and NHE2 and NHE3 on the brush border serving transcellular absorption in Na+. NHE1 and NHE2 are much more sensitive to inhibition by amiloride than NHE3, their in vitro IC50s for amiloride being 1 microM, 1 microM and 39 microM, respectively. This study tested the hypothesis that the brush border NHE3 isoform plays the predominant role in basal and meal-stimulated ileal absorption. Absorption studies (N = 72) were performed in dogs with 25-cm ileal Thiry-Vella fistulae. Six groups were studied over 4 hr. Perfusion with [14C]PEG and 140 mM Na+ was used to calculate absorption of water, ions, and glucose. Luminal amiloride was administered from the second to the fourth hours at doses of 20 microM in groups 3 and 4 to inhibit NHE1 and NHE2, and 1mM in groups 5 and 6 to also inhibit NHE3. A 480-kcal canine meal was ingested after the second hour in groups, 2, 4, and 6. Meal ingestion was followed by significant increases in water and electrolyte absorption. Amiloride (1 mM) caused significant reductions in basal and meal-stimulated ileal absorption, while the 20 microM dose had no effect on either. These data are consistent with the hypothesis that NHE3, but not NHE2, is involved in basal and meal-stimulated ileal water and Na+ absorption.
位于基底外侧膜上的NHE1调节细胞内pH值；位于刷状缘的NHE2和NHE3负责钠离子的跨细胞吸收。NHE1和NHE2比NHE3对氨氯吡脒的抑制作用更敏感，它们对氨氯吡脒的体外半数抑制浓度（IC50）分别为1微摩尔/升、1微摩尔/升和39微摩尔/升。本研究检验了以下假设：刷状缘NHE3亚型在基础状态和进食刺激后的回肠吸收中起主要作用。对72只患有25厘米回肠Thiry-Vella瘘管的犬进行了吸收研究。分六组，历时4小时进行研究。通过灌注[14C]聚乙二醇和140毫摩尔/升的钠离子来计算水、离子和葡萄糖的吸收。在第2至第4小时，第3组和第4组以20微摩尔/升的剂量给予管腔氨氯吡脒以抑制NHE1和NHE2，第5组和第6组以1毫摩尔/升的剂量给予以同时抑制NHE3。在第2小时后，第2、4和6组摄入一顿480千卡的犬粮。进食后水和电解质吸收显著增加。氨氯吡脒（1毫摩尔/升）导致基础状态和进食刺激后的回肠吸收显著降低，而20微摩尔/升的剂量对两者均无影响。这些数据与以下假设一致，即NHE3而非NHE2参与基础状态和进食刺激后的回肠水和钠离子吸收。
