STIMULATION OF BILE-ACID INDEPENDENT BILE-FLOW WITH BROMO-CYCLIC GUANOSINE-MONOPHOSPHATE

The second messenger, cyclic guanosine monophosphate (cGMP), mediates the actions of nitric oxide, natriuretic peptides, and microbial toxin s on cellular contractility and electrolyte movement. Because both hep atocellular contractility and electrolyte secretion participate in bil e formation, we investigated the actions of cGMP on this process in in tact liver. In rat liver perfused with 8-bromo-cyclic GMP (bcGMP) at 0 .5 and 3 mu mol/min, bile now increased by 5% and 31%, respectively. T he biliary excretion of the bile acid, taurocholate ([H-3]-labeled; 1 mu mol/min) and of the organic anion, bromosulfophthalein ([S-35]-labe led; tracer dose), was unchanged. The paracellular and transcytotic pa thways 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 sugg ested that the choleresis was primarily osmotic in nature. Unlike cycl ic adenosine monophosphate (cAMP), which stimulates bile acid dependen t bile now and transcytosis, bcGMP increased bile acid independent bil e flow mainly as a result of its concentrative biliary secretion.