title: Adenosine nucleotides in bile.
abstract: Activation of purinergic receptors by ATP stimulates Cl- efflux in biliary epithelial cells. To determine whether purinergic agonists are present under physiological conditions, we have assayed mammalian bile for nucleotides and assessed whether hepatoma and cholangiocarcinoma cell lines are capable of nucleotide release. Bile samples were collected from human, rat, and pig donors and assayed for nucleotide concentrations by luminometry. ATP, ADP, and AMP were present in bile from each species, and the average total nucleotide concentration in human bile was 5.21 +/- 0.91 microM (n = 16). In an in vitro model of HTC rat hepatoma cells or Mz-ChA-1 cholangiocarcinoma cells on a superfused column, nucleotides were present in the effluent from each cell type. Addition of alpha, beta-methyleneadenosine 5'-diphosphate (50 microM) to inhibit 5'-nucleotidase activity increased AMP concentrations two- to threefold. Exposure to forskolin (100 microM) or ionomycin (2 microM) stimulated nucleotide release from cholangiocarcinoma but not hepatoma cells. These studies indicate that adenosine nucleotides are present in bile in concentrations sufficient to activate purinergic receptors. Purinergic receptor activation by local nucleotide release might constitute an autocrine and/or paracrine mechanism for modulation of biliary secretion.
authors.affiliation: Department of Surgery, Duke University, North Carolina, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Chari
authors.forename: S M
authors.initials: SM
authors.lastname: Schutz
authors.forename: J E
authors.initials: JE
authors.lastname: Haebig
authors.forename: G H
authors.initials: GH
authors.lastname: Shimokura
authors.forename: P B
authors.initials: PB
authors.lastname: Cotton
authors.forename: J G
authors.initials: JG
authors.lastname: Fitz
authors.forename: W C
authors.initials: WC
authors.lastname: Meyers
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002470:Cell Survival; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D013552:Swine; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D002118:Calcium