Effects of acetazolamide on Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.
Effects of acetazolamide on Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.
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DOI：
10.1172/jci113980
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发表时间：
1989-03
期刊：
影响因子：
--
通讯作者：
M. Soleimani;P. Aronson
中科院分区：
文献类型：
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作者：
M. Soleimani;P. Aronson
我们观察了乙酰唑胺对兔肾皮质基底外侧膜泡Na+-HCO3-共转运的影响。1.2 mM乙酰唑胺不能显著降低施加向内HCO3-梯度刺激的Na+摄取，表明乙酰唑胺不直接抑制Na+-HCO3-共转运。4，4‘-二异硫氰基二苯乙烯-2，2’-二磺酸(DIDS)敏感的Na+碱共转运完全依赖于CO2/HCO3-。因此，我们测试了在某些条件下，基侧膜上对乙酰唑胺敏感的HCO3-是否可以限制钠碱共转运的速率。在存在CO2/HCO3缓冲体系但没有初始HCO3-梯度的情况下，向外的NH4+梯度刺激了5倍的Na+内流。外向NH4+梯度对Na+内流的刺激作用可被0.6 mM乙酰唑胺抑制75%以上，这表明乙酰唑胺阻断了NH4+梯度产生向内HCO3-梯度的能力。在存在向内的HCO3-梯度的情况下，向内的NH4+梯度抑制了超过70%的Na+内流。0.6 mM乙酰唑胺对Na+内流的抑制作用仅为35%，表明乙酰唑胺阻断了NH4+向内崩解HCO3-梯度的能力。类似地，在存在向内的HCO3-梯度的情况下，向外的醋酸盐梯度对Na+内流的抑制大于80%，而这种抑制被乙酰唑胺减少到仅为50%。因此，乙酰唑胺对Na+吸收的抑制或刺激取决于与pH和HCO3梯度有关的条件。乙酰唑胺与基底膜Na+-HCO3-共转运系统的间接相互作用可能是其抑制近端小管酸分泌的重要机制。
We evaluated the effects of acetazolamide on Na+-HCO3- cotransport in basolateral membrane vesicles isolated from the rabbit renal cortex. Na+ uptake stimulated by an imposed inward HCO3- gradient was not significantly reduced by 1.2 mM acetazolamide, indicating that acetazolamide does not directly inhibit Na+-HCO3- cotransport. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive Na+-base cotransport was found to be absolutely CO2/HCO3--dependent. We therefore tested whether acetazolamide-sensitive availability of HCO3- at the basolateral membrane could be rate-limiting for Na+-base cotransport under some conditions. In the presence of a CO2/HCO3- buffer system but absence of an initial HCO3- gradient, Na+ influx was stimulated fivefold by an outward NH4+ gradient. This stimulation of Na+ influx by an outward NH4+ gradient was inhibited greater than 75% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of the NH4+ gradient to generate an inward HCO3- gradient. In the presence of an inward HCO3- gradient, Na+ influx was inhibited greater than 70% by an inward NH4+ gradient. This inhibition of Na+ influx was reduced to only 35% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of NH4+ to collapse the inward HCO3- gradient. Similarly, Na+ influx in the presence of an inward HCO3- gradient was inhibited greater than 80% by an outward acetate gradient, and this inhibition was reduced to only 50% by acetazolamide. Thus, acetazolamide caused either inhibition or stimulation of Na+ uptake depending on the conditions with respect to pH and HCO3- gradients. The indirect interaction of acetazolamide with the basolateral membrane Na+-HCO3- cotransport system may be an important mechanism underlying inhibition of proximal tubule acid secretion by this agent.