Selective labeling of serotonin uptake sites in rat brain by (/sup 3/H)citalopram contrasted to labeling of multiple sites by (/sup 3/H)imipramine

Journal Article · Wed Jul 01 04:00:00 EDT 1987 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6375269

D'Amato, R J; Largent, B L; Snowman, A M; Snyder, S H

Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes (/sup 3/H)citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for (/sup 3/H)citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of (/sup 3/H)citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of (/sup 3/H)citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of (/sup 3/H)imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific (/sup 3/H)imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of (/sup 3/H)imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in (/sup 3/H)citalopram and serotonin-sensitive (/sup 3/H)imipramine binding with only a small effect on serotonin-insensitive (/sup 3/H)imipramine binding. The dissociation rate of (/sup 3/H)imipramine or (/sup 3/H)citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive (/sup 3/H)imipramine high affinity binding sites closely resembles that of (/sup 3/H)citalopram binding.

• Research Organization: Johns Hopkins Univ. School of Medicine, Baltimore, MD
• OSTI ID: 6375269
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 242:1; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
COMPARATIVE EVALUATIONS
DISTRIBUTION
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIPRAMINE
INDOLES
KINETICS
LABELLED COMPOUNDS
LABELLING
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES