Hostname: page-component-7479d7b7d-m9pkr Total loading time: 0 Render date: 2024-07-13T13:30:09.517Z Has data issue: false hasContentIssue false

The Dopamine/Neuroleptic Receptor

Published online by Cambridge University Press:  18 September 2015

Philip Seeman
Affiliation:
Department of Pharmacology, Faculty of Medicine. University of Toronto
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain. This receptor has been termed the D2 dopamine receptor, and it inhibits or interferes with dopamine-stimulated adenylate cyclase. This D2 receptor has two states, each having different affinity for dopamine. The high-affinity state, termed D2high, has a 10 nM affinity for dopamine and is the functional correlate for dopamine autoreceptors and for the dopamine receptor in the pituitary gland. The low-affinity state, termed D2low, has a 2000 nM affinity for dopamine, and may possibly represent the desensitized state of the dopamine receptor or the functional post-synaptic receptor.

Type
1. Neurotransmitters and the Pharmacology of the Basal Ganglia
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Cote, TE, Greve, CW, Kebabian, JW (1981) Stimulation of a D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland decreases the responsiveness of the beta-adrenoceptor: Biochemical mechanism. Endocrinology 108: 420426.CrossRefGoogle ScholarPubMed
Creese, I (1981) Classification of dopamine receptors. Proc. Amer. Coll. Neuropsychopharmacol. (San Diego): p. 34.Google Scholar
De Camilli, P, Macconi, D, Spada, A (1979) Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary adenomas. Nature (London) 278: 151154.CrossRefGoogle ScholarPubMed
De Lean, A, Kilpatrick, BF, Caron, MG (1982) Dopamine receptor of the porcine anterior pituitary gland: Evidence for two affinity states discriminated by both agonists and antagonists. Mol. Pharmacol. 22: 290297Google ScholarPubMed
George, S, Watanabe, M, Seeman, P (1983) Commentary: The dopamine receptor of the anterior pituitary gland. In: Dopamine Receptors, edited by Kaiser, C. and Kebabian, J., Amer. Chem. Soc. Symp. 224, Amer. Chem. Soc, Washington, pp. 9399.Google Scholar
Hamblin, MW, Creese, I (1982) 3H-Dopamine binding to rat striatal D-2 and D-3 sites: Enhancement by magnesium and inhibition by guanine nucleotides and sodium. Life Sci. 30: 15871595.CrossRefGoogle ScholarPubMed
Huff, RM, Molinoff, PB (1982) Quantitative determination of dopamine receptor subtypes not linked to activation of adenylate cyclase in rat striatum. Proc. Nat. Acad. Sci. U.S.A. 79: 75617565.CrossRefGoogle Scholar
Kebabian, JW, Calne, DB (1979) Multiple receptors for dopamine. Nature (London) 277: 9396.CrossRefGoogle ScholarPubMed
Lee, T, Seeman, P, Hornykiewicz, O, Bilbao, J, Deck, J, Tourtellotte, W (1981) Parkinson’s disease: Low density and presynaptic location of Dj dopamine receptor sites. Brain Res. 212: 494498.CrossRefGoogle Scholar
List, S, Titeler, M, Seeman, P (1979) Properties of high affinity 3H-dopamine binding sites in rat striatum. Soc. Neurosci. Abstr. 5: 654.Google Scholar
List, S, Titeler, M, Seeman, P (1980) High-affinity 3H-dopamine receptors (D3 sites) in human and rat brain. Biochem. Pharmacol. 29:16211622.CrossRefGoogle ScholarPubMed
List, S, Seeman, P (1981) Resolution of the dopamine and serotonin receptor components of 3H-spiperone binding to rat brain regions. Proc. Nat. Acad. Sci. U.S.A. 78: 26202624.CrossRefGoogle Scholar
Meunier, H, Giguere, V, Labrie, F (1980) Dopamine receptors are negatively coupled to adenylate cyclase in rat intermediate pituitary cells. Proc. 4th Int. Conf. Cyclic Nucleotides, Abstr. THA9.Google Scholar
Seeman, P (1980) Brain dopamine receptors. Pharmacol. Rev. 32:229313.Google ScholarPubMed
Seeman, P (1982) Nomenclature of central and peripheral dopaminergic sites and receptors. Biochem. Pharmacol. 31: 25632568.CrossRefGoogle ScholarPubMed
Seeman, P, Wong, M, Lee, T (1974) Dopamine receptor-block and nigral fiber impulse blockade by major tranquilizers. Fed. Proc. 33: 246.Google Scholar
Seeman, P, Wong, M, Tedesco, J (1975a) Tranquilizer receptors in rat striatum. Soc. Neurosci. Abstr. 1: 405.Google Scholar
Seeman, P, Chau-Wong, M, Tedesco, J, Wong, K (1975b) Brain receptors for antipsychotic durgs and dopamine: Direct binding assays. Proc. Nat. Acad. Sci. U.S.A. 72: 43764380.CrossRefGoogle Scholar
Seeman, P, Ulpian, C, Wells, J (1982) Dopamine receptor parameters (detected by 3H-spiperone) depend on tissue concentration. Soc. Neurosci. Abstr. 8: 718.Google Scholar
Sibley, DR, De Lean, A, Creese, I (1982) Anterior pituitary dopamine receptors. Demonstraton of interconvertable high and low affinity states of the D-2 dopamine receptor. J. Biol. Chem. 257:63516358.CrossRefGoogle Scholar
Sokoloff, P, Martres, MP, Schwartz, JC (1980) 3H-Apomorphine labels both dopamine post-synaptic receptors and autoreceptors. Nature 288: 283286.CrossRefGoogle Scholar
Stoof, JC, Kebabian, JW (1981) Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294: 366368.CrossRefGoogle ScholarPubMed
Wreggett, KA, George, SR, Seeman, P (1982) Modulation of the D2 dopamine receptor in calf caudate by guanine nucleotide. Soc. Neurosci. Abstr. 8: 719.Google Scholar
Wreggett, KA, Seeman, P (1983a) Classification and agonist requirements of dopamine receptors. Acta. Pharmaceut. Suppl. 1: 3040.Google Scholar
Wreggett, KA, Seeman, P (1983b) Agonist high- and low-affinity states of the D2 dopamine receptor in calf brain: Partial conversion by guanine nucleotide. Mol. Pharmacol., in press.Google Scholar
Zahniser, NR, Molinoff, PB (1978) Effect of guanine nucleotides in striatal dopamine receptors. Nature (London) 275: 453455.CrossRefGoogle ScholarPubMed