Inhibition of renal 11beta-hydroxysteroid dehydrogenase in vivo by carbenoxolone in the rat and its relationship to sodium excretion.
Inhibition of renal 11beta-hydroxysteroid dehydrogenase in vivo by carbenoxolone in the rat and its relationship to sodium excretion.
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甘苯索隆对大鼠体内肾 11β-羟基类固醇脱氢酶的抑制及其与钠排泄的关系。
DOI：
10.1042/cs0950435
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发表时间：
1998
期刊：
影响因子：
6
通讯作者：
Robert J. Unwin
中科院分区：
文献类型：
--
作者：
Kj Sewell;D.;AE Michael;A. Thompson;D. Norgate;Robert J. Unwin
1. The type 2 isoform of 11beta-hydroxysteroid dehydrogenase, an enzyme which converts cortisol or corticosterone to inactive 11-ketosteroid metabolites, is thought to be responsible for preventing access of endogenous glucocorticoids to mineralocorticoid receptors in the distal nephron; although direct in vivo evidence for this is still lacking. We have examined whether graded inhibition of renal 11beta-hydroxysteroid dehydrogenase activities in vivo results in corresponding changes in urinary electrolyte excretion due to exposure of mineralocorticoid receptors to circulating endogenous glucocorticoids.2. Anaesthetized rats were infused intravenously with vehicle alone or with one of three doses of carbenoxolone: 0.06, 0.6 or 6 mg/h. After measurement of renal electrolyte excretion, the kidneys were snap-frozen in liquid nitrogen and 11beta-hydroxysteroid dehydrogenase activities were measured directly by enzyme assay in the presence of NAD+ or NADP+.3. A dose-dependent inhibition of renal 11beta-hydroxysteroid dehydrogenase activities was observed: the low, intermediate and high doses of carbenoxolone causing approximately 50%, 80% and >90% inhibition respectively. Only with the high dose was an effect on renal function observed (decreased fractional Na+ excretion and urinary Na+/K+ ratio).4. The poor correlation between the extent of inhibition of renal 11beta-hydroxysteroid dehydrogenase and altered urinary Na+ excretion, apparent at the lower doses of carbenoxolone, suggests either that 11beta-hydroxysteroid dehydrogenase has considerable functional reserve, or that it may not be the only mechanism determining mineralocorticoid receptor specificity in the distal nephron.
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DOI：
10.1016/s0021-9258(18)82044-0
发表时间：
1993-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
E. Rusvai;A. Náray-Fejes-Tóth
通讯作者：
E. Rusvai;A. Náray-Fejes-Tóth
DOI：
10.1016/s0021-9258(18)47142-6
发表时间：
1994-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. K. Agarwal;T. Mune;T. Mune;C. Monder;P. White
通讯作者：
A. K. Agarwal;T. Mune;T. Mune;C. Monder;P. White
醛固酮的代谢衍生物。
DOI：
10.1152/ajprenal.1987.252.3.f365
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Morris,DJ;Brem,AS
通讯作者：
Brem,AS
11 β-OHSD 抑制剂卡苯索隆可通过醛固酮和 11-脱氧皮质酮增强钠保留。
DOI：
10.1152/ajprenal.1990.258.3.f756
发表时间：
1990
期刊：
The American journal of physiology
影响因子：
--
作者：
Morris,DJ;Souness,GW
通讯作者：
Souness,GW
影响因子：
15.9
作者：
FIELD, MJ;STANTON, BA;GIEBISCH, GH
通讯作者：
GIEBISCH, GH