The role of D-1 and D-2 receptors

Schächter, M; Bédard, Paul J.; Debono, A G; Jenner, Peter; Marsden, C. D.; Price, Paul A.; Parkes, J. D.; Keenan, John P.; Smith, Brian L.; Rosenthaler, J.; Horowski, R.; Dorow, R.

doi:10.1038/286157a0

Cited by 123 publications

(18 citation statements)

References 29 publications

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“…It seems worth mentioning here that subsets of'classi cal' receptors have been described and are now commonly accepted: (3,-and (^-adrener gic receptors [56,61]; a r and a2-adrencrgic receptors [17a. 48] and D,-and D>-dopamine receptors [54,73]. Other subclassifications were, so far, only hypothesized like those of the muscarinic receptors [7,44] and the opioid receptors [58.…”

Section: Discussionmentioning

confidence: 99%

Evidence for and against Heterogeneity in the Histamine H<sub>2</sub>-Receptor Population

Bertaccini¹,

Coruzzi²

1981

Pharmacology

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Evidence for and against heterogeneity in the histamine H₂-receptor population is reported: it was based on different degrees of potency and also of efficacy among the H₂-receptor-selective agonists; less striking but still evident differences in the potency of H₂-antagonists; atypical interactions between H₂-agonists and antagonists in particular experimental conditions and finally inability of H₁- and H₂-receptor antagonists to block some of the effects of histamine. Binding studies gave equivocal results. All the data reported in this review suggest that, although it is premature to speak about H₂-receptor subtypes, further investigations are needed to check whether or not H₂- and perhaps also H₁-receptors represent homogeneous populations of histamine receptors.

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Section: Discussionmentioning

confidence: 99%

Evidence for and against Heterogeneity in the Histamine H<sub>2</sub>-Receptor Population

Bertaccini¹,

Coruzzi²

1981

Pharmacology

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“…Thus, the therapeutic efficacy of an antipsychotic drug correlates with its antagonist affinity for the D2 receptor (3). Similarly, the motor, endocrine, and antiparkinsonian effects of ergot derivatives, such as bromocryptine, are believed to result from stimulation of D2 receptors (4). Recent studies, however, suggest that D1 receptors in the brain may have important functions.…”

mentioning

confidence: 99%

Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission.

Fremeau

Duncan

Fornaretto

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

285

140

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Expression of a DI dopamine receptor was examined in the rat brain by using a combination of in situ hybridization and in vitro receptor autoradiography. Cells expressing DI receptor mRNA were localized to many, but not all, brain regions receiving dopaminergic innervation. The highest levels of hybridization were detected in the caudateputamen, nucleus accumbens, and olfactory tuberde. Cells expressing DI receptor mRNA were also detected throughout the cerebral cortex, limbic system, hypothalamus, and thala- The diverse physiological effects of dopamine in the mammalian brain are mediated by receptors, which have been classically subdivided on the basis of pharmacological, biochemical, and functional differences into two subtypes referred to as D1 and D2 (1). Activation of D1 receptors, which are the most abundant dopamine receptor subtype in brain, stimulates adenylyl cyclase activity (1). Activation of D2 receptors inhibits adenylyl cyclase activity and increases K+ channel conductance (2).Traditionally, the behavioral actions of dopaminergic agents have been attributed to interaction with D2 receptors, whereas the role of D1 receptors in the central nervous system has been less clear. Thus, the therapeutic efficacy of an antipsychotic drug correlates with its antagonist affinity for the D2 receptor (3). Similarly, the motor, endocrine, and antiparkinsonian effects of ergot derivatives, such as bromocryptine, are believed to result from stimulation of D2 receptors (4). Recent studies, however, suggest that D1 receptors in the brain may have important functions. D1 receptor activation has been reported to inhibit neurite outgrowth and neuronal growth cone motility (5), regulate cerebral glucose utilization (6), inhibit serotonin release in the substantia nigra (7), stimulate 'y-aminobutyric acid release in the substantia nigra (8) and striatum (9)

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“…At present, the functional role of each receptor sonian effects via D,-receptor stimulation (Schachter et al, 1980; Controls are lesioned rats treated with saline (n = 6). The experimental groups consist of lesioned rats treated with SKF-38393 or LY-17 1555 (n = 3) at the indicated doses.…”

mentioning

confidence: 99%

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

Trugman¹,

Wooten²

1987

J. Neurosci.

153

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he relative roles of D1 and D2 dopamine receptor stimulation in mediating the antiparkinsonian effects of dopaminergic drugs remain unclear. To determine the functional metabolic consequences of selective dopamine receptor stimulation, we used 2-deoxyglucose (2-DG) autoradiography to examine the effects of the D1 agonist SKF-38393 and the D2 agonist LY-171555 on regional cerebral glucose utilization (RCGU) in rats with unilateral 6-hydroxydopamine (6-OHDA) substantia nigra lesions. SKF-38393 (0.5-25.0 mg/kg) and LY-171555 (0.01-5.0 mg/kg) produced indistinguishable behavioral responses, including vigorous contralateral rotation. Treatment with each drug similarly increased glucose utilization, dose-dependently, in the parafascicular thalamus, subthalamic nucleus, deep layers of the superior colliculus, and lateral midbrain reticular formation ipsilateral to the nigral lesion; glucose utilization was decreased in the ipsilateral lateral habenula. By contrast, the D1 and D2 agonists differentially altered glucose utilization in the entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNr). SKF-38393, 5.0 and 25.0 mg/kg, increased glucose utilization 127 and 275%, respectively, in the pars reticulata ipsilateral to the lesion. LY-171555, 1.0 and 5.0 mg/kg, caused maximal contralateral turning, yet did not alter glucose utilization in the ipsilateral SNr. The glucose utilization response of the ipsilateral EP paralleled that of the SNr demonstrating large increases following administration of SKF-38393 and minimal change following the use of LY-171555. The results demonstrate that the selective D1 agonist reproduces the marked glucose utilization increases (2-3-fold above control values) in the EP and SNr that were previously observed using L-DOPA and apomorphine in this model, whereas the selective D2 agonist does not.(ABSTRACT TRUNCATED AT 250 WORDS)

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The role of D-1 and D-2 receptors

Cited by 123 publications

References 29 publications

Evidence for and against Heterogeneity in the Histamine H<sub>2</sub>-Receptor Population

Evidence for and against Heterogeneity in the Histamine H<sub>2</sub>-Receptor Population

Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission.

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

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