Secretin receptors in a new preparation of plasma membranes from intrahepatic biliary epithelium.

Journal Article

Secretin is thought to cause choleresis by acting on a receptor expressed by bile duct epithelial cells. In this study, the receptor was characterized using a new preparation of intrahepatic bile duct plasma membranes. Hyperplastic biliary trees were obtained from 3-week bile duct-ligated rats. The biliary trees were homogenized, filtered, and subjected to an aqueous two-phase partition technique to yield highly purified plasma membranes (confirmed by a 14-fold enrichment in gamma-glutamyl transpeptidase activity and a 10-fold enrichment in 125I-secretin binding). 125I-secretin bound saturably with high affinity and in a dose-dependent fashion (Kd = 1.3 +/- 0.1 nM, Bmax = 273 +/- 23 fmole/mg) to purified plasma membranes. The binding characteristics of secretin were most consistent with a single site receptor model. Competitive binding studies indicated that the secretin-related peptides glucagon, peptide histidine isoleucine, gastric inhibitory peptide, and growth hormone releasing factor did not inhibit binding. Vasoactive intestinal peptide (1 microM) reduced maximal binding by 19 +/- 1%. The GTP analogs guanylylimidodiphosphate and guanosine 5'-O-[3-thiotriphosphate] (1 microM) inhibited binding by 16 +/- 2 and 13 +/- 1%, respectively. In conclusion, secretin binds to a specific, high-affinity receptor in intrahepatic bile duct epithelium that is coupled to a G-protein-linked signal transduction system.

Full Text

Duke Authors

Cited Authors

  • Farouk, M; Vigna, SR; Haebig, JE; Gettys, TW; McVey, DC; Chari, R; Pruthi, RS; Meyers, WC

Published Date

  • January 1, 1993

Published In

Volume / Issue

  • 54 / 1

Start / End Page

  • 1 - 6

PubMed ID

  • 8094102

International Standard Serial Number (ISSN)

  • 0022-4804

Digital Object Identifier (DOI)

  • 10.1006/jsre.1993.1001

Language

  • eng

Conference Location

  • United States