Allosteric Inhibition as a Model to Explain Flatter Displacement Curves in Binding Experiments: Application to ‘Heterogeneous’ Serotonin Receptors

Abstract

Flattened or biphasic inhibition curves are usually interpreted by postulating the presence of two sites which are labelled with the same affinity by the ligand and can be recognized using the appropriate inhibitor with different selective affinities.

We found that a priori this type of curve, can be equally fitted by another model, the allosteric model, on account of the mathematical equivalence of the two model functions when the 3H-ligand concentration is kept constant (i. e. inhibition experiments). A new approach consisting of three-dimensional analysis of the experimental data (3H-ligand binding as a function of ligand and inhibitor concentrations, simultaneously) permitted a statistical discrimination between the two models.

The examples, used as tool for the present study, are the flattened or biphasic inhibition curves obtained by displacing 3H-serotonin with the neuroleptic spiperone.

The results are discussed in relation to the general Interpretation of this type of “anomalous” binding data and to the specific field of serotonergic receptor subtypes.