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药物缀合物的胆汁和尿液排泄:利尿和利胆对大鼠硫酸去甲骆驼蓬碱和去甲骆驼蓬碱葡糖醛酸苷排泄的影响。

Biliary and urinary excretion of drug conjugates: effect of diuresis and choleresis on excretion of harmol sulphate and harmol glucuronide in the rat.

作者信息

Jorritsma J, Meerman J H, Vonk R J, Mulder G J

出版信息

Xenobiotica. 1979 Apr;9(4):247-52. doi: 10.3109/00498257909038727.

DOI:10.3109/00498257909038727
PMID:483860
Abstract
  1. Harmol (7-hydroxy-1-methyl-9H-pyrido [3,4b] indole) is converted to harmol sulphate and harmol glucuronide in the rat in vivo. Harmol sulphate is excreted mainly in urine, while harmol glucuronide is excreted about equally in bile and urine, when harmol is given intravenously. 2. In rats with ligated kidneys, only choleresis produced by glycodehydrocholate and dehydrocholate caused enhanced biliary excretion of harmol sulphate; harmol glucuronide was unaffected. Several other bile salts had no effect. 3. Mannitol diuresis markedly increased urinary excretion of harmol sulphate, and decreased its biliary excretion. Harmol glucuronide was much less affected. 4. Nafenopin pretreatment increased liver weight and bile flow, and enhanced biliary excretion of harmol sulphate at the expense of its urinary excretion. 5. For harmol sulphate, urine and bile are compensatory pathways of elimination that can be influenced by urine and bile flow changes through diuresis and choleresis.
摘要
  1. 哈尔莫(7-羟基-1-甲基-9H-吡啶并[3,4b]吲哚)在大鼠体内会转化为硫酸哈尔莫和哈尔莫葡糖醛酸。静脉注射哈尔莫时,硫酸哈尔莫主要经尿液排泄,而哈尔莫葡糖醛酸在胆汁和尿液中的排泄量大致相等。2. 在结扎肾脏的大鼠中,只有甘氨脱氧胆酸盐和脱氧胆酸盐引起的胆汁分泌增加会导致硫酸哈尔莫的胆汁排泄增强;哈尔莫葡糖醛酸不受影响。其他几种胆汁盐则无作用。3. 甘露醇利尿显著增加了硫酸哈尔莫的尿液排泄,并减少了其胆汁排泄。哈尔莫葡糖醛酸受影响程度小得多。4. 萘酚平预处理增加了肝脏重量和胆汁流量,并增强了硫酸哈尔莫的胆汁排泄,同时减少了其尿液排泄。5. 对于硫酸哈尔莫而言,尿液和胆汁是相互补偿的排泄途径,可通过利尿和胆汁分泌的变化所引起的尿液和胆汁流量改变而受到影响。

相似文献

1
Biliary and urinary excretion of drug conjugates: effect of diuresis and choleresis on excretion of harmol sulphate and harmol glucuronide in the rat.药物缀合物的胆汁和尿液排泄:利尿和利胆对大鼠硫酸去甲骆驼蓬碱和去甲骆驼蓬碱葡糖醛酸苷排泄的影响。
Xenobiotica. 1979 Apr;9(4):247-52. doi: 10.3109/00498257909038727.
2
Cholestatic effect of harmol glucuronide in the rat. Prevention of harmol-induced cholestasis by increased formation of harmol sulfate.Harmol葡糖醛酸苷在大鼠中的胆汁淤积作用。通过增加Harmol硫酸盐的形成预防Harmol诱导的胆汁淤积。
J Pharmacol Exp Ther. 1982 Jun;221(3):731-4.
3
The availability of inorganic sulphate in blood for sulphate conjugation of drugs in rat liver in vivo. (35S)Sulphate incorporation into harmol sulphate.大鼠肝脏在体内进行药物硫酸结合反应时血液中无机硫酸盐的可用性。(35S)硫酸盐掺入哈尔莫硫酸盐。
Biochem J. 1978 May 15;172(2):247-51. doi: 10.1042/bj1720247.
4
Secretion of the organic anion harmol sulfate from liver into blood. Evidence for a carrier-mediated mechanism.肝脏中有机阴离子硫酸哈尔醇向血液的分泌。载体介导机制的证据。
Biochem Pharmacol. 1985 Jun 15;34(12):2129-35. doi: 10.1016/0006-2952(85)90406-x.
5
Metabolism of harmol and transport of harmol conjugates in isolated rat hepatocytes.去甲骆驼蓬碱在离体大鼠肝细胞中的代谢及去甲骆驼蓬碱缀合物的转运
Drug Metab Dispos. 1983 Sep-Oct;11(5):433-40.
6
Sulphate and glucuronic acid conjugation of harmol in human fetal and adult liver tissue.去甲骆驼蓬碱在人胎儿及成人肝脏组织中的硫酸化和葡萄糖醛酸化结合反应
Dev Pharmacol Ther. 1982;5(1-2):14-20.
7
Effect of nafenopin (SU-13437) on liver function. Influence on the hepatic transport of phenolphthalein glucuronide and chlorothiazide.萘酚平(SU - 13437)对肝功能的影响。对酚酞葡萄糖醛酸苷和氯噻嗪肝转运的影响。
Drug Metab Dispos. 1976 Mar-Apr;4(2):107-11.
8
Aberrant Pharmacokinetics of harmol in the perfused rat liver preparation: sulfate and glucuronide conjugations.灌注大鼠肝脏制剂中去甲骆驼蓬碱的异常药代动力学:硫酸化和葡萄糖醛酸化结合反应
J Pharmacol Exp Ther. 1981 Oct;219(1):134-40.
9
UDP glucuronyltransferase and phenolsulfotransferase from rat liver in vivo and in vitro--IV. Species differences in harmol conjugation and elimination in bile and urine in vivo.大鼠肝脏UDP葡糖醛酸基转移酶和酚磺基转移酶的体内外研究——IV. 体内胆汁和尿液中去甲骆驼蓬碱结合与消除的种属差异
Biochem Pharmacol. 1975 Aug 15;24(16):1481-4. doi: 10.1016/0006-2952(75)90022-2.
10
Normal and retrograde perfusion to probe the zonal distribution of sulfation and glucuronidation activities of harmol in the perfused rat liver preparation.采用正向和逆向灌注法,探究灌注大鼠肝脏制剂中去甲骆驼蓬碱硫酸化和葡萄糖醛酸化活性的区域分布。
J Pharmacol Exp Ther. 1983 Mar;224(3):647-53.

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