Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-19T12:23:51.209Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical Importance of D-1 and D-2 Receptors

Published online by Cambridge University Press:  05 January 2016

Michèle Beaulieu
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 existence of subtypes of dopamine receptors as defined by Kebabian and Calne is now well accepted. The Dl receptor is typically associated with stimulation of adenylate cyclase, while the D2 receptor is either independent of adenylate cyclase or mediates its inhibition. Considerable interest has been generated by the potential physiological and clinical roles of these receptor subtypes. Availability of agonists and antagonists specifically acting at the D1 or D2 receptor site has stimulated research to characterize the functional effects of each receptor subtype. This might facilitate the development of effective compounds to control the signs and symptoms of Parkinson's disease and perhaps prevent the induction of debilitating side effects. Recent evidence indicates that Dl receptor stimulation is required to obtain full expression of the D2 receptor site, which has typically been associated with the clinical benefits of dopaminergic therapy. Both pre- and postsynaptic location of the receptors must also be taken into consideration as well as involvement of other neuronal systems. It appears that in PD, progressive involvement of the dopaminergic pathways is the principal pathological course, however, noradrenergic and serotonergic pathways are likewise involved. This multineuronal involvement suggests that drugs acting specifically at receptor sites, located on both pre- and postsynaptic neurons, might be required at different times during the course of the disease process to control its symptoms and/or the complications occurring after long-term treatment with a given drug.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 402 - 406
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Barbeau, A.Preliminary observation on abnormal catecholamine metabolism in basal ganglia disease. Neurology 1960; 10:446–451.CrossRefGoogle Scholar
2.Birkmayer, W, Hornykiewicz, O.Der L-3,4-dihydroxyphenylalanin (Dopa) - Effekt bei der Parkinson akinese. Wien Klin Wschr 1961; 73: 787–795.Google Scholar
3.Kebabian, JW, Calne, DB.Multiple receptors for dopamine. Nature 1979; 277: 93–96.CrossRefGoogle ScholarPubMed
4.Côté, TE, Grewe, CW, Tsuruta, K, et al. D2 dopamine receptormediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires GTP. Endocrinology 1982; 110: 812–819.CrossRefGoogle Scholar
5.Kebabian, JW, Beaulieu, M, Itoh, Y.Pharmacological and biochemical evidence for the existence of two categories of dopamine receptor. Can J Neurol Sci 1984; 11:114–117.CrossRefGoogle ScholarPubMed
6.Seeman, P, Watanabe, M, Grigoriadis, D, et al. Dopamine D2 receptor binding sites for agonists, a tetrahedral model. Molec Pharmacol 1985; 28: 391–399.Google ScholarPubMed
7.Seeman, P.Brain dopamine receptors. Pharmacol Rev 1980; 32: 229–313.Google ScholarPubMed
8.Grigoriadis, D, Seeman, P.The dopamine/neuroleptic receptor. Can J Neurol Sci 1984; 11: 108–113.CrossRefGoogle ScholarPubMed
9.Leff, SE, Creese, I.Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum. Evidence that [3H] dopamine can label a high affinity agonist-binding state of the Dl dopamine receptor. Molec Pharmacol 1985: 27: 184–192.Google Scholar
10.Fuxe, K.Agnati, LF, Kalia, M, et al. Dopaminergic systems in the brain and pituitary. In: Flückiger, E, Miiller, EE, Thorner, MO, eds. Basic and clinical aspects of neuroscience. The dopaminergic system. Berlin: Springer-Verlag, 1985: 11–25.Google Scholar
11.Stoof, JC.Dopamine receptors in the striatum: biochemical and physiological studies. In: Kaiser, C, Kebabian, JW, eds. Dopamine receptors, American Chemical Society Symposium Series 224. Washington: American Chemical Society Press, 1983: 117–145.Google Scholar
12.Nomoto, M, Jenner, P and Marsden, CD.The dopamine D2 agonist LY 141865, but not the Dl agonist SKF 38393, reverses parkinsonism induced by l–methyl–4–phenyl–l ,2,3,6–tetrahydropyridine (MPTP) in the common marmoset. Neurosci Let 1985:57: 37–41.CrossRefGoogle ScholarPubMed
13.Bédard, PJ, Di Paolo, T, Falardeau, P, et al. Chronic treatment with L-Dopa, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H] spiperone binding. Brain Res. 1986; 379: 294–299.CrossRefGoogle Scholar
14.Stoof, JC, Kebabian, JW.Opposing roles for Dl and D2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 1981; 294: 366–368.CrossRefGoogle Scholar
15.Rosengarten, M, Schweitzer, JW, Friedhoff, AJ.Induction of oral dyskinesias in naive rats by Dl stimulation. Life Sciences 1983; 33: 2479–2482.CrossRefGoogle Scholar
16.Mashurano, M, Waddington, JL.Stereotyped behaviour in response to the selective D2 dopamine receptor agonist RU 24213 is enhanced by pretreatment with the selective Dl agonist SK&F 38393. Neuropharmacology 1986; 25: 947–949.CrossRefGoogle Scholar
17.Molloy, AG, Waddington, JL.Sniffing, rearing and locomotor responses to the Dl dopamine agonist R-SK&F 38393 and to apomorphine: differential interactions with the selective Dl and D2 antagonists SCH 23390 and metoclopramide. Eur J Pharmacol 1985; 108: 305–308.CrossRefGoogle Scholar
18.Gropetti, A, Flauto, C, Parati, A, et al. Dopamine receptor changes in response to prolonged treatment with L-Dopa. J Neural Transm 1986; 22: 33–45.Google Scholar
19.Goldstein, M, Lieberman, A, Meller, E.A possible molecular mechanism for the antiparkinsonian action of bromocriptine in combination with levodopa. Trends Pharmacol Sci 1985; 6: 436–437.CrossRefGoogle Scholar
20.Robertson, HA, Robertson, GS.A possible role for both Dl and D2 receptors? The antiparkinson action of bromocriptine in combination with levodopa. Trends Pharmacol Sci 1986; 7: 224–225.CrossRefGoogle Scholar
21.Robertson, GS, Robertson, HA.Synergistic effects of Dl and D2 dopamine agonists on turning behaviour in rats. Brain Res 1986; 384: 387–390.CrossRefGoogle Scholar
22.Carlson, JH, Bergstrom, DA, Walters, JR.Stimulation of both Dl and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists : a neurophysio-logical study. Brain Res 1987; 400: 205–218.CrossRefGoogle Scholar
23.Pimoule, C, Shoemaker, H, Reynolds, GP, et al. [3H]SCH23390 labelled DI dopamine receptors are unchanged in schizophrenia and Parkinson’s disease. Eur J Pharmacol 1985; 114: 235–237.CrossRefGoogle Scholar
24.Shibuya, M.Dopamine-sensitive adenylate cyclase activity in the striatum in Parkinson’s disease. J Neurol Transm 1979; 44: 287–295.CrossRefGoogle ScholarPubMed
25.Lee, T, Seeman, P, Rajput, A, et al. Receptor basis for dopaminergic supersensitivity in Parkinson’s disease. Nature 1978; 273:59–61.Google ScholarPubMed
26.Rinne, U, Lonnberg, P, Koskinen, V.Dopamine receptors in the parkinsonian brain. J Neurol Transm 1981; 51: 97–106.CrossRefGoogle ScholarPubMed
27.Olsen, R, Reisine, T, Yamamura, H.Neurotransmitter receptors: Biochemistry and alterations in neuropsychiatrie disorders. Life Sci 1980; 27: 801–808.CrossRefGoogle Scholar
28.Quik, M, Spokes, E, Mackay, A, et al. Alterations in 3H-spiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy-Drager syndrome and Parkinson’s disease. J Neurol Sci 1979; 43: 429–437.CrossRefGoogle Scholar
29.Bokobza, F, Ruberg, M, Scatton, B.et al. [3H]-spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 1984; 99: 167–175.CrossRefGoogle Scholar
30.Guttman, M, Seeman, P.Dopamine D2 receptor density in parkinsonian brain is constant for duration of disease, age, and duration of L-Dopa therapy. Advances in neurology 1986: 45: 51–57.Google Scholar
31.Hornykiewicz, O, Kish, SJ.Biochemical pathophysiology of Parkinson’s Disease. Advances in Neurology 1986: 45: 19–34.Google Scholar
32.Creese, I, Snyder, SH.Nigrostriatal lesions enhance striatal [3H] apomorphine and [3H] spiroperidol binding. Eur J Pharmacol 1979; 56: 277–281.CrossRefGoogle ScholarPubMed
33.Rinne, UK, Rinne, JO, Rinne, JK, et al. Brain receptor changes in Parkinson’s disease in relation to the disease process and treatment. J Neural Transm 1983; 18: 279–286.Google Scholar
34.Rinne, UK.Combined bromocriptine-levodopa therapy early in Parkinson’s disease. Neurology 1985; 35: 1196–1198.CrossRefGoogle ScholarPubMed
35.Larsen, AT, Newman, R, Lewitt, P, et al. Severity of Parkinson’s disease and the dosage of bromocriptine. Neurology 1984; 34: 795–797.CrossRefGoogle ScholarPubMed
36.Riopelle, RJ.Bromocriptine and the clinical spectrum of Parkinson’s Disease. Submitted to Can I Neurol Sci.Google Scholar
37.Farley, IJ, Hornykiewicz, O.Noradrenaline in subcortical brain regions of patients with Parkinson’s disease and control subjects. In: Advances in parkinsonism, Birkmayer, W, Hornykiewicz, O, eds., Editiones Roche, Basel 1976: 178–185.Google Scholar
38.Scatton, B, Javoy-Agid, F, Rouquier, L, et al. Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 1983; 275: 321–328.CrossRefGoogle ScholarPubMed