Adenosine nucleotides in bile.
Chari, Ravi S., S. M. Schutz, J. E. Haebig, Gayle H. Shimokura, Peter
B. Cotton, J. Gregory Fitz, and William C. Meyers.
Departments of Surgery and Medicine, Duke University and Durham VA
Medical Centers, Durham, N.C., 27710
APStracts 2:0166G, 1995.
Activation of purinergic receptors by ATP stimulates Cl- efflux in
biliary epithelial cells. In order to determine whether purinergic
agonists are present under physiologic 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 [mu]M (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 [mu]M) to inhibit 5'
nucleotidase activity increased AMP concentrations 2- to 3-fold.
Exposure to forskolin (100 [mu]M) or ionomycin (2 [mu]M) stimulated
nucleotide release from cholangiocarcinoma but not hepatoma cells.
These studies indicate that adenine nucleotides are present in bile
in concentrations sufficient to activate purinergic receptors.
Purinergic receptor activation by local nucleotide release might
constitute an autocrine/paracrine mechanism for modulation of biliary
secretion.
Received 24 February 1995; accepted in final form 2 August 1995.
APS Manuscript Number G79-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.