Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules
Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules
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DOI：
10.1046/j.1523-1755.2000.00933.x
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发表时间：
2000-03-01
影响因子：
19.6
通讯作者：
Soleimani, M
中科院分区：
文献类型：
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作者：
Ali, R;Amlal, H;Soleimani, M
背景：研究表明，糖皮质激素可促进近端小管对HCO3的重吸收。功能和分子水平的研究表明，HCO3-在近端肾小管的重吸收是通过管腔H+-ATPase和Na+/H+交换器(NHE-3)，以及底侧Na+：HCO3-共转运体(NBC)的串联作用来实现的。本实验旨在观察肾上腺类固醇激素对大鼠肾近端小管NBC-1和NHE-3表达及活性的影响。分别皮下注射地塞米松(100mU/d)或醋酸脱氧皮质酮(30 mg/kg)、强效糖皮质激素或盐皮质激素类似物。2~4天后处死动物，检测皮质和近端小管中NBC-1和NHE-3mRNA的表达和活性。Northern杂交结果显示，地塞米松处理4天(N=6，P=0.03)的大鼠皮质NBC-1mRNA表达增加约92%，但不增加2天。NHE-3mRNA表达无明显变化。NBC和NHE-3活性的测量分别是在HCO3-存在或不存在的情况下，NBC和NHE-3从酸负荷中恢复到依赖于Na的pH(I)，以及在近端小管悬液中负载BCECF的合适的抑制剂。地塞米松治疗4天(P<；0.01，N=5)的大鼠的NBC活性增加了约80%，但不是2天。地塞米松治疗2天和4天后，NHE-3活性分别比对照组增加34%和42%(P<；0.05和P<；0.02)。醋酸脱氧皮质酮治疗不会改变NBC-1的表达。药物浓度的糖皮质激素可增强肾近端小管NBC-1的基因表达和功能活性。NBC和NHE-3活性增强可导致近端小管HCO3重吸收增加，并有助于维持与糖皮质激素产生相关的病理生理状态中的代谢性碱中毒。
Background, Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H+-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- co-transporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules.Methods. Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules.Results. Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pH(i) recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs, control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression.Conclusion. Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.