Smith J J, Welsh M J
Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
J Clin Invest. 1993 Apr;91(4):1590-7. doi: 10.1172/JCI116365.
An understanding of the fluid and electrolyte transport properties of any epithelium requires knowledge of the direction, rate, and regulation of fluid transport and the composition of the fluid. Although human airway epithelial likely play a key role in controlling the quantity and composition of the respiratory tract fluid, evidence for such a role is not available. To obtain such knowledge, we measured fluid and electrolyte transport by cultured human nasal epithelia. Under basal conditions we found that epithelia absorbed Na+ and fluid; both processes were inhibited by addition of amiloride to the mucosal surface. These data suggest that active Na+ absorption is responsible for fluid absorption. Interestingly, Na+ absorption was not accompanied by the net absorption of Cl-; some other anion accompanied Na+. The combination of cAMP agonists and mucosal amiloride stimulated the secretion of NaCl-rich fluid. But surprisingly, the response to cAMP agonists in the absence of amiloride showed substantial intersubject variability: cAMP stimulated fluid secretion across some epithelia, for others, cAMP stimulated fluid absorption. The explanation for the differences in response is uncertain, but we speculate that the magnitude of apical membrane Na+ conductance may modulate the direction of fluid transport in response to cAMP. We also found that airway epithelial secrete H+ and absorb K+ under basal conditions; both processes were inhibited by cAMP agonists. Because the H+/K(+)-ATPase inhibitor, SCH 28080, inhibited K+ absorption, an apical membrane H+/K(+)-ATPase may be at least partly responsible for K+ and H+ transport. However, H+/K+ exchange could not entirely account for the luminal acidification. The finding that cAMP agonists inhibited luminal acidification may be explained by the recent finding that cAMP increases apical HCO3- conductance. These results provide new insights into how the intact airway epithelium may modify the composition of the respiratory tract fluid.
要了解任何上皮组织的液体和电解质转运特性，需要掌握液体转运的方向、速率和调节机制以及液体的成分。尽管人类气道上皮细胞可能在控制呼吸道液体的数量和成分方面发挥关键作用，但尚无证据支持这一作用。为了获得此类知识，我们测量了培养的人鼻上皮细胞的液体和电解质转运。在基础条件下，我们发现上皮细胞吸收Na⁺和液体；向黏膜表面添加氨氯吡脒会抑制这两个过程。这些数据表明，Na⁺的主动吸收是液体吸收的原因。有趣的是，Na⁺的吸收并未伴随Cl⁻的净吸收；有其他一些阴离子伴随Na⁺。cAMP激动剂与黏膜氨氯吡脒的组合刺激了富含NaCl的液体分泌。但令人惊讶的是，在没有氨氯吡脒的情况下，对cAMP激动剂的反应在个体间存在很大差异：cAMP刺激了一些上皮细胞的液体分泌，而对另一些上皮细胞，cAMP刺激了液体吸收。反应差异的原因尚不确定，但我们推测顶端膜Na⁺电导的大小可能会调节对cAMP反应时液体转运的方向。我们还发现，气道上皮细胞在基础条件下分泌H⁺并吸收K⁺；这两个过程均受到cAMP激动剂的抑制。由于H⁺/K⁺-ATP酶抑制剂SCH 28080抑制了K⁺的吸收，顶端膜H⁺/K⁺-ATP酶可能至少部分负责K⁺和H⁺的转运。然而，H⁺/K⁺交换并不能完全解释管腔酸化现象。cAMP激动剂抑制管腔酸化这一发现，可能可以用最近发现的cAMP增加顶端HCO₃⁻电导来解释。这些结果为完整的气道上皮细胞如何改变呼吸道液体成分提供了新的见解。
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