Protein tyrosine kinase and PI3-K participate in the inhibitory effect of insulin-like growth factor I on basolateral 10 pS Chloride channels in the thick ascending limb of the rat kidney

作     者：Li-Jun WANG~1,Shu-Min KONG~1,Wen-Nan LI~1,Hong-Yu SUI~1,Peng WU~1,Ming-Xiao WANG~1,Yu-Jie LIU~1, Li-Li FAN~1,Li GU~1,Wen-Hui WANG~2,Rui-Min GU~(1,*) 1 Department of Pharmacology,Harbin Medical University,Harbin 150081,China 2 Department of Pharmacology,New York Medical College,Valhalla,New York,USA 

会议名称：《中国生理学会第23届全国会员代表大会暨生理学学术大会》

会议日期：2010年

学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.30570673 and No.30770800) 

关 键 词：C1 transport insulin-like growth factor I protein tyrosine kinase phosphatidylinositol 3-kinase thick ascending limb 

摘      要：正Insulin-like growth factorⅠ（IGF-I） plays an important role in accelerating protein and carbohydrate metabolism, and affects cell proliferation,differentiation and inhibiting apoptosis in a long *** to IGF-I and IGF-I receptor are distributed in the basolateral and apical membrane of the thick ascending limb,IGF-I could influence sodium chloride （NaCl） transport in this nephron *** a 10 pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment,thus we performed patch-clamp technique in cell-attached patches to study the effect of IGF-I on the basolateral 10 pS Cl channels in the thick ascending limb of the rat *** of IGF-I inhibited the basolateral 10 pS Cl channels,significantly decreased channel activity（a product of channel number and open probability）.The inhibitory effect of IGF-I is not mediated by protein tyrosine phosphatase or phospholipase C-dependent mechanisms,because blocking protein tyrosine phosphatase with phenylarsine oxide or inhibition of phospholipase C with U73122 did not abolish the inhibitory effect of IGF-I on the 10 pS Cl ***,inhibition of protein tyrosine kinase with Herbinmycin A or Genistein or repression of phosphatidylinositol 3-kinase（PI3-K） with Wortmannin abolished the effect of IGF-I,this suggests that protein tyrosine kinase and PI3-K are responsible for mediating the effect of IGF-I on the 10 pS Cl *** studies show that inhibition of basolateral 10 pS Cl channels by IGF-I is mediated by stimulating protein tyrosine kinase,which in turn stimulates PI3-K in the thick ascending limb of the rat kidney.