St-Pierre M V, Dufour J F, Arias I M
Department of Physiology, Tufts University School of Medicine, Boston, MA, USA.
Hepatology. 1996 Dec;24(6):1487-91. doi: 10.1002/hep.510240631.
The second messenger, cyclic guanosine monophosphate (cGMP), mediates the actions of nitric oxide, natriuretic peptides, and microbial toxins on cellular contractility and electrolyte movement. Because both hepatocellular contractility and electrolyte secretion participate in bile formation, we investigated the actions of cGMP on this process in intact liver. In rat liver perfused with 8-bromo-cyclic GMP (bcGMP) at 0.5 and 3 micromol/min, bile flow increased by 5% and 31%, respectively. The biliary excretion of the bile acid, taurocholate ([3H]-labeled; 1 micromol/min) and of the organic anion, bromosulfophthalein ([35S]-labeled; tracer dose), was unchanged. The paracellular and transcytotic pathways of biliary excretion, assessed by horseradish peroxidase (HRP), were unaffected. BcGMP was concentratively secreted into bile and the accompanying 30% increase in the biliary clearance of erythritol suggested that the choleresis was primarily osmotic in nature. Unlike cyclic adenosine monophosphate (cAMP), which stimulates bile acid dependent bile flow and transcytosis, bcGMP increased bile acid independent bile flow mainly as a result of its concentrative biliary secretion.
第二信使环磷酸鸟苷（cGMP）介导一氧化氮、利钠肽和微生物毒素对细胞收缩性及电解质转运的作用。由于肝细胞收缩性和电解质分泌均参与胆汁形成，我们研究了cGMP在完整肝脏中对这一过程的作用。在以0.5和3微摩尔/分钟的速度灌注8-溴环磷酸鸟苷（bcGMP）的大鼠肝脏中，胆汁流量分别增加了5%和31%。胆汁酸牛磺胆酸盐（[3H]标记；1微摩尔/分钟）和有机阴离子溴磺酞（[35S]标记；示踪剂量）的胆汁排泄未发生变化。通过辣根过氧化物酶（HRP）评估的胆汁排泄的细胞旁和跨细胞途径未受影响。BcGMP被浓缩分泌到胆汁中，伴随而来的赤藓糖醇胆汁清除率增加30%表明胆汁分泌增加主要是渗透性的。与刺激胆汁酸依赖性胆汁流量和跨细胞转运的环磷酸腺苷（cAMP）不同，bcGMP增加胆汁酸非依赖性胆汁流量主要是由于其浓缩的胆汁分泌。
