Biochemical properties of D1 and D2 dopamine receptors.

Abstract

The physiological action of dopamine are mediated by two distinct subtypes of receptors, D1 and D2 dopamine receptors. D1-receptors are linked to stimulation of adenylate cyclase whereas D2-receptors inhibit the enzyme and may also couple to other signal transduction systems such as ion channels. In order to characterize these receptors at the biochemical level we have developed specific probes for the identification and purification of these proteins. The ligand binding sites of the two receptors have been identified by photoaffinity labeling and reside on distinct polypeptides. In rat striatum, the D1 receptor binding site can be identified as a peptide of Mr = 72,000. In contrast, the D2 receptors appears to reside on an Mr = 94,000 peptide in most tissues. A larger peptide of Mr = 120,000 identified in the intermediate lobe of pituitary may represent the unproteolyzed form of this receptor. An affinity chromatography purification procedure has been developed for the D2 dopamine receptor. This procedure affords a substantial purification (greater than 1000 fold) of the receptor solubilized from bovine anterior pituitary glands with complete retention of its binding properties. These biochemical tools should eventually lead to the complete characterization of these two receptor subtypes.