title: Influence of agonist induced internalization on [3H]Ro15-4513 binding-an application to imaging fluctuations in endogenous GABA with positron emission tomography.
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.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College, London, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Quelch
authors.forename: Vittorio
authors.initials: V
authors.lastname: De Santis
authors.forename: Annette
authors.initials: A
authors.lastname: Strege
authors.forename: James
authors.initials: J
authors.lastname: Myers
authors.forename: Lisa
authors.initials: L
authors.lastname: Wells
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.forename: Christine
authors.initials: C
authors.lastname: Parker
authors.forename: Robin
authors.initials: R
authors.lastname: Tyacke
mesh_terms: D000818:Animals; D001386:Azides / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D000078308:Tiagabine; D014316:Tritium / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001386:Azides; D002250:Carbon Radioisotopes; D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; C042957:Ro 15-4513; D000078308:Tiagabine
keywords: GABAA; PET; [11C]Ro15-4513; internalization; neurotransmitters