Dopamine Receptors in Human and Calf Brains, Using [3H]apomorphine and an Antipsychotic Drug

In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor.