Role of assay conditions in determining agonist potency at D2 dopamine receptors in striatal homogenates

Brain Res. 1986 Jul;387(1):29-35. doi: 10.1016/0169-328x(86)90017-3.

Abstract

The affinity of dopamine agonists for rat striatal D2 receptors labelled by [3H]spiperone was enhanced by 5 and 10 mM magnesium ions. Preparation and assay of membranes with 10 mM magnesium ions yielded displacement data better described by a model where agonists competed for [3H]spiperone at two sites. The high affinity component (Kd 0.2-10 nM) accounted for 80% of the total sites and 100 microM guanosine-5'-triphosphate shifted 25-30% of the sites to a low affinity form, independent of the agonist. These data are consistent with the D2 receptor being coupled to a guanine nucleotide regulatory protein, with the proportion of high affinity agonist sites being influenced by membrane preparation procedures, magnesium ions and guanosine-5'-triphosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Binding, Competitive
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Guanosine Triphosphate / pharmacology
  • Haloperidol / pharmacology
  • Kinetics
  • Magnesium / pharmacology
  • Male
  • Radioligand Assay / methods
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Spiperone / metabolism

Substances

  • Receptors, Dopamine
  • Spiperone
  • Guanosine Triphosphate
  • Magnesium
  • Haloperidol
  • Apomorphine
  • Dopamine