Localization and characterization of secretin binding sites expressed by rat bile duct epithelium.
The goal of the present studies was to identify and characterize the site of secretin action in the liver. Sections of normal and bile duct-ligated rat livers were used for in vitro 125I-secretin receptor autoradiography. Saturable binding was observed in both normal and bile duct-ligated livers but was much greater in the bile duct-ligated preparations. Binding was limited to biliary epithelium and the increased secretin binding observed in the ligated livers correlated with the increase in ductular tissue. Saturable binding was inhibited in a dose-dependent fashion by increasing concentrations of nonradioactive secretin. Analysis of saturation binding showed that 125I-secretin binding was best fit by a one-site receptor model with a Kd of 5.3 +/- 1.1 nmol/L. Glucagon, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, growth hormone-releasing hormone, and cholecystokinin did not inhibit saturable 125I-secretin binding at concentrations of 1 pmol/L to 1 mumol/L. The authors conclude that high-affinity, specific secretin binding sites are present in rat intrahepatic biliary epithelium. When bile ducts are stimulated to proliferate by bile duct ligation, secretin binding is also increased.
Farouk
M
M
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Vigna
S R
SR
McVey
D C
DC
Meyers
W C
WC
D000818:Animals; D001345:Autoradiography; D001652:Bile Ducts / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006965:Hyperplasia / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000096:biosynthesis*; D012633:Secretin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D002766:Cholecystokinin; D013007:Growth Hormone-Releasing Hormone