药物代谢酶的分子遗传学

药物代谢酶的分子遗传学3

蔡卫民　张银娣1

(南京军区南京总医院临床药理科,南京　210002)

中国图书分类号　R345;R966;R968

文献标识码A　文章编号100121978(1999)0620491206

摘要　综述近10年来国内外有关药物代谢酶的分子遗传学进展,介绍药物代谢酶的基本概念并重点探讨了具有遗传多态性的两种氧化酶(细胞色素P450酶CYP2D6,CYP2C19)和一种结合酶(N2乙酰化转移酶)的个体和种族差异。最后主要讨论了表型分型和基因分型在药物代谢酶研究中的一些应用。

关键词　药物代谢;分子遗传学;细胞色素P450;N2乙酰化1998212223收稿,1999203212再修回

3国家人事部留学回国人员基金资助课题

1南京医科大学临床药理研究所,南京　210029

作者简介:蔡卫民,男,40岁,博士生,副主任药师;

张银娣,女,62岁,教授,博士生导师,临床药理专业委员

会委员,药物代谢专业委员会委员转移酶;遗传多态性;表型分型;基因分型;人类

分子遗传学与药理学尤其是药物代谢研究有着密切的关系,药物代谢酶活性在不同种族、不同人群中的个体差异受遗传因素和环境因素共同影响。其中遗传因素影响表现在体内关键代谢酶的基因发生变化,导致其表达的蛋白质在结构、功能和活性上发生改变。本文就近10年来国内外分子遗传学在药物代谢酶研究的一些最新进展作一回顾。

1　药物代谢与药物代谢酶

大多数药物为脂溶性的弱电解质化合物,进入体内后均需进行生物转化,生成极性较大的化合物而易于从肾脏和胆汁排泄。生物转化一般为灭活反应,使药物的作用和毒性减弱或消失;但也有些药物的代谢物仍有活性或活性更强;还有些药物本身并无活性,只有经过体内代谢后生成活性代谢物起作

C alcium2activated chloride channel on smooth muscle cell membrane

WAN G Ze2J un,YU De2Jie,DEN G Yan2Chun,BAO Guang2Hong

(Instit ute of B asic Medical Sciences Chi nese A cadem y of Medical Sciences

Schoole of B asic Medici ne Peki ng U nion Medical College,Beiji ng　100005)

ABSTRACT　Calcium2activated chloride channel ex2 isted on several kind of smooth muscle cells.The nec2 essary condition for activating calcium activated chlorede channel is intracellular calcium[Ca2+]i level rising.Both potassium channel and chloride channel are activated by several kind of activators induced cal2 cium releasing from calcium store.The threshold val2 ues for activating I Cl(Ca)are differente from animal categories and ing flourometric measure2 ment of[Ca2+]i of rat portacaval smooth muscle cells get that least[Ca2+]i value of activated I K(Ca)should be considered more than70～80nmol・L-1.This val2 ue is smaller than the least[Ca2+]i of180nmol・L-1 of I Cl(Ca),therefore considered that I K(Ca)is more sensitive than that of I Cl(Ca)for[Ca2+]i.I Cl(Ca)is ac2 tivated by[Ca2+]i rising resulting from extracellular calcium pass through the voltage dependent calcium channels.Because of IP3is activated by G protein coupling with some receptor,so that I Cl(Ca)is activat2 ed.According to analyse whole cell currents,the conductance of I Cl(Ca)should be considered smaller than10pS.The chloride equilibrium potential(ECl) of smooth muscle cells is more positive than resting membrane potential.The chloride outflow from chlo2 ride channels opening,which promote membrane po2 tential approaching to ECl,therefore membrane de2 polarizing.When the calcium activated cholride chan2 nels are opening the cell membrane depolarized,so that induced cells exciting.This channel plays an im2 portant role during smooth muscle cells exciting which induced by hormones and neuro2transmiters. KEY WORDS　smooth muscle cell;calcium2activated chloride channel

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中国药理学通报　Chinese Pharm acological B ulletin　1999Dec;15(6):491～6