Synthesis and characterization of a new labeled gastrin ligand, 125-I-BH-[Leu15]-gastrin-(5-17), on binding to canine fundic mucosal cells and Jurkat cells

Int J Pept Protein Res. 1994 Oct;44(4):348-56. doi: 10.1111/j.1399-3011.1994.tb01019.x.

Abstract

In the course of our study concerning gastrin and cholecystokinin (CCK) receptors, we have synthesized and characterized a new labeled gastrin ligand, 125I-BH-[Leu15]-gastrin-(5-17) [(3-[125I]iodo-4-hydroxyphenyl)-propionyl-[Leu15]-gastrin-(5-17)]. Binding of 125I-BH-[Leu15]-gastrin-(5-17) to isolated canine fundic mucosal cells was specific, saturable and of high affinity. 125I-BH-[Leu15]-gastrin- (5-17) and 125I-BH-CCK-8[(3-[125I]iodo-4-hydroxyphenyl)-propionyl-CCK-8] interact with isolated canine fundic mucosal cells with small differences in maximal binding capacities and affinities, 3800 +/- 900 binding sites/cell (Kd = 0.52 +/- 0.23 nM) and 6200 +/- 1100 binding sites/cell (Kd = 0.31 +/- 0.18 nM), respectively. The relative order of potencies for gastrin and CCK analogs in displacing 125I-BH-[Leu15]-gastrin-(5-17) binding correlated well with those obtained using 125I-BH-CCK-8. Selective CCK/gastrin antagonists L-364,718 (MK-329) and L-365,260 also inhibited 125I-BH-[Leu15]-gastrin-(5-17) binding. These results indicate that 125I-BH-[Leu15]-gastrin-(5-17) binds to gastrin receptors in isolated canine fundic mucosal cells. We have also characterized 125I-BH-[Leu15]-gastrin-(5-17) binding to the human Jurkat lymphoblastic cell line (Jurkat cells) known to express the CCK-B/gastrin receptor. Saturation experiments have shown that both 125I-BH-[Leu15]-gastrin-(5-17) and 125I-BH-CCK-8 interact with a single class of high-affinity binding sites in the Jurkat cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzodiazepinones / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cholecystokinin / antagonists & inhibitors
  • Devazepide
  • Dogs
  • Gastric Fundus / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Gastrins / chemical synthesis*
  • Gastrins / metabolism*
  • Gastrins / pharmacology
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Molecular Sequence Data
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Phenylurea Compounds*
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Sincalide / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Temperature

Substances

  • 3-(3-iodo-4-hydroxyphenyl)propionyl(Leu(15))gastrin-(5-17)
  • Benzodiazepinones
  • Gastrins
  • Iodine Radioisotopes
  • Peptide Fragments
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • L 365260
  • Cholecystokinin
  • Devazepide
  • Sincalide
  • Calcium