Wang T, Malnic G, Giebisch G, Chan Y L
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Clin Invest. 1993 Jun;91(6):2776-84. doi: 10.1172/JCI116519.
Bicarbonate transport was studied in vivo by separate microperfusion experiments of early and late distal tubules. Total CO2 was measured by microcalorimetry and fluid absorption by 3H-inulin. Significant bicarbonate absorption was observed in all experimental conditions. Bicarbonate transport was load-dependent upon increasing the luminal bicarbonate concentration from 15 to 50 mM in both early and late distal tubule segments and remained constant at higher concentrations at a maximum rate of 100-110 pmol/min per mm. At low lumen bicarbonate concentrations (15 mM), higher rates of bicarbonate absorption were observed in early (32.9 +/- 4.57 pmol/min per mm) as compared to late distal tubules (10.7 +/- 3.1 pmol/min per mm). Amiloride and ethyl-isopropylamiloride both inhibited early but not late distal tubule bicarbonate absorption whereas acetazolamide blocked bicarbonate transport in both tubule segments. Fluid absorption was significantly reduced in both tubule segments by amiloride but only in early distal tubules by ethyl-isopropylamiloride. Substitution of lumen chloride by gluconate increased bicarbonate absorption in late but not in early distal tubules. Bafilomycin A1, an inhibitor of H-ATPase, inhibited late and also early distal tubule bicarbonate absorption, the latter at higher concentration. After 8 d on a low K diet, bicarbonate absorption increased significantly in both early and late distal tubules. Schering compound 28080, a potent H-K ATPase inhibitor, completely blocked this increment of bicarbonate absorption in late but not in early distal tubule. The data suggest bicarbonate absorption via Na(+)-H+ exchange and H-ATPase in early, but only by amiloride-insensitive H+ secretion (H-ATPase) in late distal tubules. The study also provides evidence for activation of K(+)-H+ exchange in late distal tubules of K depleted rats. Indirect evidence implies a component of chloride-dependent bicarbonate secretion in late distal tubules and suggests that net bicarbonate transport at this site results from bidirectional bicarbonate movement.
通过早期和晚期远端小管的单独微灌注实验，对体内的碳酸氢盐转运进行了研究。通过微量量热法测量总二氧化碳，并通过3H-菊粉测量液体吸收。在所有实验条件下均观察到显著的碳酸氢盐吸收。在早期和晚期远端小管段中，随着管腔碳酸氢盐浓度从15 mM增加到50 mM，碳酸氢盐转运依赖于负荷，并且在更高浓度下以100 - 110 pmol/min每毫米的最大速率保持恒定。在低管腔碳酸氢盐浓度（15 mM）时，与晚期远端小管（10.7 +/- 3.1 pmol/min每毫米）相比，早期（32.9 +/- 4.57 pmol/min每毫米）观察到更高的碳酸氢盐吸收率。氨氯吡脒和乙基异丙基氨氯吡脒均抑制早期但不抑制晚期远端小管的碳酸氢盐吸收，而乙酰唑胺则阻断两个小管段的碳酸氢盐转运。氨氯吡脒使两个小管段的液体吸收显著降低，但乙基异丙基氨氯吡脒仅使早期远端小管的液体吸收降低。用葡萄糖酸盐替代管腔中的氯离子可增加晚期但不增加早期远端小管的碳酸氢盐吸收。H-ATP酶抑制剂巴弗洛霉素A1抑制晚期和早期远端小管的碳酸氢盐吸收，对后者的抑制作用在较高浓度时出现。在低钾饮食8天后，早期和晚期远端小管的碳酸氢盐吸收均显著增加。强效H-K ATP酶抑制剂先灵化合物28080完全阻断晚期但不阻断早期远端小管中碳酸氢盐吸收的这种增加。数据表明，早期通过Na(+)-H+交换和H-ATP酶吸收碳酸氢盐，但晚期远端小管仅通过对氨氯吡脒不敏感的H+分泌（H-ATP酶）吸收。该研究还为低钾大鼠晚期远端小管中K(+)-H+交换的激活提供了证据。间接证据表明晚期远端小管中存在氯离子依赖性碳酸氢盐分泌成分，并表明该部位的净碳酸氢盐转运是由双向碳酸氢盐移动产生的。
