cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.
cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.
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cGMP 刺激不依赖胆汁酸的胆汁形成和胆汁碳酸氢盐排泄。
DOI：
10.1152/ajpgi.1996.270.3.g418
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Sawkat-Anwer,M
中科院分区：
文献类型：
--
作者：
Myers,NC;Grune,S;Jameson,HL;Sawkat-Anwer,M
在离体灌流的大鼠肝脏和大鼠肝细胞上研究了环磷酸鸟苷（cGMP）对肝胆汁形成的影响。在离体灌流大鼠肝脏中的研究表明，输注8-溴鸟苷3 '，5'-环一磷酸（8-BrcGMP，3 μ mol/min或100 μ M）1）增加胆汁流量，但不影响同时输注的牛磺胆酸盐的胆汁排泄，2）增加胆汁浓度和HCO 3（-）的排泄，但不影响谷胱甘肽的胆汁排泄，（3）增加灌流液H+净流出量而不影响肝脏O2摄取。在离体大鼠肝细胞中的研究表明：1）8-BrcGMP在存在下增加细胞内pH（但不存在）细胞外HCO-3的作用，并且4，4 ' -二异硫氰基芪-2，2'-二磺酸和Na+替代抑制该作用，2）8-BrcGMP不影响牛磺胆酸盐摄取和细胞内[Ca 2 +]，和3）胆汁酸，如熊去氧胆酸盐和胆酸盐，不增加细胞cGMP。总之，这些结果表明cGMP刺激胆汁酸非依赖性胆汁形成，部分是通过刺激胆汁HCO 3-排泄。cGMP可能通过刺激窦状隙Na+ -HCO 3-共转运而增加HCO 3-排泄，但不通过Na+/H+交换。cGMP不像3 '，5'-环磷酸腺苷，可能不调节肝牛磺胆酸盐转运，胆汁酸诱导的富HCO 3胆汁分泌可能不通过cGMP介导。
The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.