Quantitative in vivo receptor binding. III. Tracer kinetic modeling of muscarinic cholinergic receptor binding

Journal Article · Tue Oct 01 00:00:00 EDT 1985 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.82.19.6711· OSTI ID:6182001

Frey, K A; Hichwa, R D; Ehrenkaufer, R L; Agranoff, B W

A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term ''free receptor density'' is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of (TH)scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period.

• Research Organization: Univ. of Michigan, Ann Arbor
• OSTI ID: 6182001
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 19; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BLOOD-BRAIN BARRIER
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ESTERS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATHEMATICAL MODELS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
POSITRON COMPUTED TOMOGRAPHY
QUATERNARY COMPOUNDS
RADIONUCLIDE KINETICS
RATS
RECEPTORS
RODENTS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRITIUM COMPOUNDS
VERTEBRATES