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家兔近端小管对有机阳离子N1-甲基烟酰胺的转运。II. 离体灌注小管中的重吸收和分泌

Transport of the organic cation N1-methylnicotinamide by the rabbit proximal tubule. II. Reabsorption and secretion in the isolated perfused tubule.

作者信息

Besseghir K, Chatton J Y, Roch-Ramel F

机构信息

Institut de Pharmacologie de l'Université de Lausanne, Switzerland.

出版信息

J Pharmacol Exp Ther. 1990 May;253(2):452-60.

PMID:1971015
Abstract

The mechanisms involved in the transport of the organic cation N1-methylnicotinamide (NMN) were investigated in the isolated perfused rabbit S2 proximal tubule. NMN underwent a small reabsorptive transport which appeared to be passive. NMN secretory transport was saturable, inhibited by mepiperphenidol (10(-4) M) and presented a relatively low apparent affinity (apparent Km of 852 microM) for the organic cation transport system, with transport against a concentration gradient being observed only at low flow rates. Acidification of the perfusate, by either buffering it at pH 6.8 with MES, or by bubbling the bath with a mixture of 80% O2-20% CO2, resulted in a decrease, rather than an increase, of NMN secretion. Carbonic anhydrase inhibition with ethoxyzolamide (10(-4) M in the bath) did not modify NMN secretion. Addition of 20 to 40 microM NMN in the perfusate also did not change NMN secretion. Proton or organic cation counterexchange seemed therefore not to play a major role in NMN apical step of secretion, the basolateral step appearing to be the general organic cation system of transport for which NMN shows a low affinity.

摘要

在离体灌注的兔S2近端小管中研究了有机阳离子N1-甲基烟酰胺(NMN)的转运机制。NMN进行了少量的重吸收转运,这似乎是被动的。NMN的分泌性转运是可饱和的,受美哌隆(10⁻⁴ M)抑制,并且对有机阳离子转运系统表现出相对较低的表观亲和力(表观Km为852 μM),仅在低流速下观察到逆浓度梯度的转运。通过用MES将灌注液缓冲至pH 6.8或用80% O₂-20% CO₂的混合气体鼓泡浴使灌注液酸化,导致NMN分泌减少而非增加。用乙氧唑胺(浴中10⁻⁴ M)抑制碳酸酐酶不会改变NMN的分泌。在灌注液中添加20至40 μM NMN也不会改变NMN的分泌。因此,质子或有机阳离子反向交换似乎在NMN分泌的顶端步骤中不起主要作用,基底外侧步骤似乎是NMN显示低亲和力的一般有机阳离子转运系统。

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