Absolute abundances and affinity states of dopamine receptors in mammalian brain: A review

The abundances of dopamine (DA) D1 and D2 receptors have been assayed with radioligands in membrane preparations and by autoradiography in vitro, and also in living brain using positron emission tomography (PET). This review compares the saturation binding parameters (Bmax and KD) obtained in striatum by these several methods, and in different species. Some uncertainty in quantitation is derived from the incomplete specificities of commonly used ligands, especially Sch 23,390 for D1 sites and spiperone for D2‐like sites. In striatal membrane preparations, the D1 Bmax ranges from 10 to 139 pmol g−1 tissue, whereas the D2 Bmax ranges from 8 to 42 pmol g−1 tissue. Receptor concentrations in human material, despite the more extended post mortem interval, are roughly similar to those reported in rodent and nonhuman primate. Estimates of Bmax by quantitative autoradiography are generally five times higher than corresponding results for similar ligands in membrane preparations. The saturation binding parameters in living striatum have been estimated by serial PET studies with ligands over a range of specific activities. The few PET estimates of D1 Bmax, (40–80 pmol g−1) and numerous PET estimates of D2 Bmax (20–40 pmol g−1) are in general agreement with membrane estimates, but fall far short of the mean of autoradiographic results in vitro. Apparent affinities for D1 and D2 ligands in vivo are typically 10 times lower than for corresponding in vitro studies, presumably because the unbound ligand concentration is not corrected for the free fraction in living brain tissue. The disparate Bmax results by method suggest the presence of a large reservoir or reserve of D1 and D2 receptors in intact brain sections, which are unavailable to PET ligands in vivo, and which may be lost during the preparation of washed membranes. A subset of receptors existing in a high affinity state for agonists is detected in washed membrane preparations, in which the coupling to intracellular G‐proteins may have become artificially limiting. However, in most PET and autoradiographic studies in vitro, agonist and antagonist ligands have similar Bmax. Discrepancies in the literature highlight the need for a better understanding of affinity states in vivo and trafficking of G‐protein coupled receptors between plasma membrane and intracellular compartments. Synapse, 2011. © 2011 Wiley‐Liss, Inc.