Summary:The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cel lular substrates. Evidence also exists that these pro cesses also occur for f)-adrenergic, muscarinic cholin ergic, and a-opiate receptors in frog erythrocytes or cul tured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recy cling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine an tagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatumThe ability of neurons to modulate the number and function of receptors at the synapse is impor tant for the regulation of neuronal activity in re sponse to varied afferent stimulation. The results of pharmacological and lesion studies suggest that mechanisms exist to regulate receptor number in order to preserve homeostasis. Denervation or chronic receptor blockade with antagonist drugs in creases receptor number. Conversely, chronic re ceptor stimulation with either agonist drugs or neu rotransmitter-releasing drugs results in reduced re ceptor number. The total number of receptors changes very slowly, however, in response to chronic alterations in ligand concentration. This suggests that these changes in receptor number are the result of altered biosynthesis and/or degrada tion of the receptors. The slow response of neuro transmitter receptor number to alterations in stimu lation, as well as the slow net turnover rate of these receptors, has encouraged the general notion that the postsynaptic membrane is static with regard to insertion and removal of receptors.However, the number of receptors at the synapse may be altered rapidly not by altering the total number of receptors, but by altering the distribu tion of receptors between the cell surface and intra cellular pools. Rapid receptor internalization has been demonstrated for a variety of nonneuronal re ceptors, such as those for low density lipoprotein, insulin, transferrin, asialoglycoprotein, and epi dermal growth factor (for review, see Goldstein et ai. , 1979; Wileman et ai. , 1985). Recently, evidence has emerged that receptors for neurotransmitters redistribute between the cell surface and intracel-292 D. C. CHUGANI ET AL. lular pools. For example, incubation of frog eryth rocytes and human astrocytoma cells with the (3-ad renergic agonist, isoproterenol, results in rapid functional desensitization accompanied by a shift of 50%-60% of surface (3-adrenergic receptors to an intracellular pool with no decrease in the total number of receptors (Chuang and Costa, 1979; Harden et aI., 1980; Stadel et aJ., 1983; lnsel et aI., 1983...
