Development of a Radioligand Binding Assay for 5-HT4 Receptors in Guinea-pig and Rat Brain

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1993 Jul 1

PMID 8358562

Citations 57

Authors

C J Grossman

G J Kilpatrick

K T Bunce

Affiliations

Soon will be listed here.

Abstract

1. The 5-HT4 receptor antagonist, GR113808, has been radiolabelled to a high specific activity with tritium. 2. Characterization of specific [3H]-GR113808 binding in homogenates of guinea-pig striatum and hippocampus revealed a single site of high affinity (Kd values 0.20 and 0.13 nM respectively). 3. [3H]-GR113808 binding was reversible and displayed rapid kinetics such that association and dissociation were complete within 3 min. 4. Specific [3H]-GR113808 binding was potently and stereoselectively inhibited by agonists and antagonists acting at the 5-HT4 receptor but not by compounds selective for other 5-HT receptors or other neurotransmitter receptors. 5. Autoradiographic analysis revealed a discrete localization in both guinea-pig and rat brain with high concentrations of binding in brain areas such as the striatum, substantia nigra and olfactory tubercle. 6. [3H]-GR113808 binding to homogenates of guinea-pig striatum meets the criteria for labelling of the 5-HT4 receptor and, as such, represents the first characterization of this receptor in a radioligand binding assay.

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