In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization.
The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [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 striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.
Chugani
D C
DC
Department of Pharmacology, UCLA School of Medicine.
Ackermann
R F
RF
Phelps
M E
ME
D000818:Animals; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008474:Medial Forebrain Bundle / Q000502:physiology; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012039:Regional Blood Flow; D013134:Spiperone / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013378:Substantia Nigra / Q000502:physiology; D014316:Tritium
D003902:Detergents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D014316:Tritium; D013134:Spiperone; D004298:Dopamine