title: cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.
abstract: 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.
authors.affiliation: Department of Veterinary Medicine, Tufts University, School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Myers
authors.forename: S
authors.initials: S
authors.lastname: Grune
authors.forename: H L
authors.initials: HL
authors.lastname: Jameson
authors.forename: M
authors.initials: M
authors.lastname: Sawkat-Anwer
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000378:metabolism / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D001647:Bile Acids and Salts; D013873:Thionucleotides; D001127:Arginine Vasopressin; C016276:8-bromocyclic GMP; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D013656:Taurocholic Acid; D014580:Ursodeoxycholic Acid; D000584:Amiloride; D000242:Cyclic AMP; D005978:Glutathione; D006152:Cyclic GMP; D002794:Choline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine