Solubilisation of high-affinity dopamine receptors

Abstract

NEUROLEPTIC drugs are thought to act by blocking brain dopamine receptors¹. In vitro binding assays using either ³H-haloperidol^2,3 or ³H-spiperone^4,5 have provided more direct evidence of this interaction. Although spiperone has been reported to label serotonergic receptors in the frontal cortex⁶, in the rat striatum, in both in vitro^4–9 and in vivo conditions^5,10,11, the binding characteristics of this drug are dopaminergic. Initial attempts to solubilise the neuroleptic receptor were recently undertaken in our laboratory, but the ³H-spiperone macromolecular complex obtained from rat striatal membranes after digitonin treatment¹² did not show the original highaffinity binding characteristics for dopamine agonists and antagonists except for spiperone itself. More recently, solubilised neuroleptic sites were found in digitonin extracts from calf caudate but they were still not characterised¹³. We now report the solubilisation of binding sites from dog striatum which retain the characteristics of membrane-bound dopamine receptors.