Characterization of kinin binding sites: identity of B2 receptors in the epithelium and the smooth muscle of the guinea pig ileum

Can J Physiol Pharmacol. 1991 Jun;69(6):818-25. doi: 10.1139/y91-123.

Abstract

Binding of [125I-Tyr8]bradykinin (BK) was measured in homogenates of epithelial and smooth muscle layers of the guinea pig ileum. Binding assays were performed at 4 degrees C for 40 min (smooth muscle) or 90 min (epithelium) in 25 mM PIPES buffer at pH 6.8 in the presence of 1 mM 1,10-phenanthroline, 140 micrograms/mL bacitracin, 1 mM captopril, 1 mM dithiothreitol, and 0.1% bovine serum albumin. Specific binding of [125I-Tyr8]BK (0.32 nM) to epithelial and smooth muscle cell membranes was linearly related to protein concentration between 0.05 and 0.5 mg/mL. Equilibrium experiments showed that specific binding of [125I-Tyr8]BK was saturable and Scatchard analysis indicated the presence of a high affinity site with a Kd value of 1.6 nM and a Bmax of 156 fmol/mg of protein in the epithelial cell membranes. In smooth muscle membranes, Kd was 1.8 nM and the maximum number of binding sites was 58 fmol/mg of protein. Unlabelled peptides, namely bradykinin, [Tyr8]BK, [Hyp3]BK, D-Arg[Hyp3]BK, [Hyp3,Tyr(Me8)]BK, and kallidin displaced [125I-Tyr8]BK binding while other peptides, angiotensin II and substance P, had no effect. A series of B2-receptor antagonists displaced [125I-Tyr8]BK from specific binding sites with IC50 values ranging from 16 to 152 nM on epithelial cell membranes; similar values were obtained from smooth muscle cell membranes. These findings suggest that the binding sites in both preparations are of the B2 type. B1-receptor agonists and antagonists were found to be inactive at concentrations up to 10(-4) M. Results obtained in the two preparations were compared and a positive highly significant correlation was demonstrated between the two sets of data.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Bradykinin / analogs & derivatives
  • Bradykinin / metabolism
  • Bradykinin / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Epithelium / metabolism
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / metabolism
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Jugular Veins / drug effects
  • Jugular Veins / physiology
  • Kallidin / metabolism
  • Kinetics
  • Ligands
  • Male
  • Muscle, Smooth / metabolism*
  • Peptides / metabolism
  • Rabbits
  • Receptors, Bradykinin
  • Receptors, Neurotransmitter / metabolism*

Substances

  • Iodine Radioisotopes
  • Ligands
  • Peptides
  • Receptors, Bradykinin
  • Receptors, Neurotransmitter
  • bradykinin, Tyr-
  • Kallidin
  • Bradykinin