Influence of agonist induced internalization on [3H]Ro15-4513 binding-an application to imaging fluctuations in endogenous GABA with positron emission tomography

Synapse. 2015 Jan;69(1):60-5. doi: 10.1002/syn.21780. Epub 2014 Sep 19.

Abstract

Low affinity α1/α2 containing GABAA receptors are significantly less able to bind [(11) C]/[(3) H]Ro15-4513 following translocation to the endosomal environment. The alterations in [(11) C]Ro15-4513 binding observed in vivo following perturbations in endogenous GABA are likely driven by both alterations in receptor binding parameters following agonist induced internalisation and the GABA Shift.

Keywords: GABAA; PET; [11C]Ro15-4513; internalization; neurotransmitters.

MeSH terms

  • Animals
  • Azides / pharmacokinetics*
  • Benzodiazepines / pharmacokinetics*
  • Binding, Competitive
  • Carbon Radioisotopes / pharmacokinetics
  • Cell Membrane / diagnostic imaging
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • GABA-A Receptor Antagonists / pharmacology*
  • Hippocampus / diagnostic imaging*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Nipecotic Acids / pharmacology*
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism
  • Tiagabine
  • Tritium / pharmacokinetics
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Azides
  • Carbon Radioisotopes
  • GABA-A Receptor Antagonists
  • Nipecotic Acids
  • Radiopharmaceuticals
  • Receptors, GABA-A
  • Tritium
  • Benzodiazepines
  • gamma-Aminobutyric Acid
  • Ro 15-4513
  • Tiagabine