Hepatic Bile Formation: Developing a New Paradigm.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Norman B Javitt
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引用次数: 0

Abstract

In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium taurocholate, and the hormone secretin to stimulate bile flow led to conflicting data and a moratorium on attempts to further develop the initial proposal. However, current data amplify the initial proposal and indicate both paracellular and transcellular water flow into hepatic ductules and the canalicular conduit in response to an osmotic gradient. Also, the need to further modify the initial proposal became apparent with the recognition that bile acid aggregates (micelles), which form in the canalicular conduit, generate lecithin-cholesterol vesicles that contain water unrelated to an osmotic gradient. As part of this development is the recent introduction of the fluorescent localization after photobleaching technique for direct determination of hepatic duct flow and clarification of the role of biomarkers such as mannitol and polyethylene glycol 900. With the new paradigm, these biomarkers may prove useful for quantifying paracellular and transcellular water flow, respectively. SIGNIFICANCE STATEMENT: It is essential to identify and characterize all the sites for water flow during hepatic bile formation to obtain more precision in evaluating the causes and possible therapeutic approaches to cholestatic syndromes. Updating the Sperber proposal provides a new paradigm that addresses the advances in knowledge that have occurred.

肝胆汁形成:发展新范式。
1959年,Ivar Sperber对比了胆汁和尿液的形成,并提出水流入小管是对渗透梯度的反应,而不是流体静力梯度。早期尝试使用胆汁酸、牛磺胆酸钠和激素分泌素来刺激胆汁流动,这导致了相互矛盾的数据,并暂停了进一步发展最初建议的尝试。然而,目前的数据强化了最初的建议,并表明细胞旁和细胞间的水都流入肝小管和小管,以响应渗透梯度。此外,随着胆汁酸聚集体(胶束)在小管导管中形成,产生卵磷脂-胆固醇囊泡,其中含有与渗透梯度无关的水,进一步修改最初建议的必要性变得明显。作为这一发展的一部分,最近引入了光漂白后荧光定位技术,用于直接测定肝管流量和澄清生物标志物(如甘露醇和聚乙二醇900)的作用。有了新的范例,这些生物标志物可能分别被证明对定量细胞旁和细胞间水流有用。意义声明:确定和表征肝胆汁形成过程中水流的所有部位对于更精确地评估胆汁淤积综合征的原因和可能的治疗方法至关重要。更新Sperber提案提供了一种新的范式,可以解决已经发生的知识进步。
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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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