Dopamine 02 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary

Yamaguchi, Hideyo; Aiba, Atsu; Nakamura, Kenji; Nakao, Kazuki; Sakagami, Hiroyuki; Goto, Kaoru; Kondo, Hisatake; Katsuki, Motoya

doi:10.1046/j.1365-2443.1996.d01-238.x

Cited by 47 publications

(30 citation statements)

References 44 publications

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“…This suggests that these two alternatively spliced variants and highly structurally homologous proteins function in a complementary and synergistic manner, rather than an antagonistic one. (2) The reduced spontaneous movement observed in D2LϪ/Ϫ mice resembles the phenotypic behavior reported in D2-null knock-out mice (which are deficient in both D2 isoforms) (Baik et al, 1995;Yamaguchi et al, 1996;Kelly et al, 1998). In particular, the locomotor activity of D2LϪ/Ϫ mice on a congenic B6 background was ϳ50% lower than that of WT mice, which is comparable with the degree of reduction in locomotion observed in D2-null knock-outs on a similar genetic background (Kelly et al, 1998).…”

Section: Discussionmentioning

confidence: 61%

“…The inhibitory effect of DA on SNc neurons is mediated specifically by D2 because it is completely blocked by D2 antagonists (Bunney et al, 1973;Pinnock, 1984;Sanghera et al, 1984;Lacey et al, 1987) and it is absent in D2-null knock-out mice (Yamaguchi et al, 1996;Mercuri et al, 1997). The inhibitory effect of DA on SNc neurons is not mediated by D3 or D4, because the effect of DA is intact in D3 knock-out mice (Koeltzow et al, 1998) and there is no detectable D4 expression in SN (Bouthenet et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…D2-null knock-out mice have been reported to exhibit stunted growth and low fertility (Baik et al, 1995;Yamaguchi et al, 1996), to have a darkened coat color (Yamaguchi et al, 1996;Kelly et al, 1997), or to have a skewed Mendelian genotype ratio of Ϫ/Ϫ mice (Kelly et al, 1997). In contrast to these observations, D2LϪ/Ϫ mice had normal fertility and body weight, in comparison with WT mice (examined up to the age of 7 months).…”

Section: Generation Of Dopamine D2l Receptor-deficient Micementioning

confidence: 95%

“…It has been well documented that dopamine exerts an inhibitory effect on SNc dopaminergic neurons and that this effect is mediated specifically by the D2 receptor (Bunney et al, 1973;Pinnock, 1984;Sanghera et al, 1984;Lacey et al, 1987;Yamaguchi et al, 1996;Mercuri et al, 1997). Spontaneous firing of SNc neurons was recorded extracellularly in brain slices Aghajanian, 1987, 1989).…”

Section: D2l-deficient Mice Express a Functional D2s Receptormentioning

confidence: 99%

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Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Wang¹,

Xu²,

et al. 2000

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The dopamine D2 receptor (D2) system has been implicated in several neurological and psychiatric disorders, such as schizophrenia and Parkinson's disease. There are two isoforms of the D2 receptor: the long form (D2L) and the short form (D2S). The two isoforms are generated by alternative splicing of the same gene and differ only by 29 amino acids in their protein structures. Little is known about the distinct functions of either D2 isoform, primarily because selective pharmacological agents are not available. We generated D2L receptor-deficient (D2LϪ/Ϫ) mice by making a subtle mutation in the D2 gene. D2LϪ/Ϫ mice (which still express functional D2S) displayed reduced levels of locomotion and rearing behavior. Interestingly, haloperidol produced significantly less catalepsy and inhibition of locomotor activity in D2LϪ/Ϫ mice. These findings suggest that D2L and D2S may contribute differentially to the regulation of certain motor functions and to the induction of the extrapyramidal side effects associated with the use of typical antipsychotic drugs (e.g., haloperidol). Quinpirole induced a similar initial suppression of locomotor activity in both D2LϪ/Ϫ and wild-type mice. In addition, the D2S receptor in the mutant mice functioned approximately equally well as did D2L as an impulse-modulating autoreceptor. This suggests that the functions of these two isoforms are not dependent on the formation of receptor heterodimers. Our findings may provide novel information for potentially developing improved antipsychotic drugs. Key words: dopamine D2L receptor; knock-out mice; locomotion; catalepsy; autoreceptor; haloperidol; D2S receptorAlterations in the dopamine D2 receptor (D2) system have been implicated in a variety of neurological and psychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention-deficit hyperactive disorder, and drug addiction (Sibley et al., 1993;Graybiel, 1995;Jaber et al., 1996;Nestler and Aghajanian, 1997;Koob et al., 1998). Parkinsonian patients exhibit deficits in motor function, which are attributed to the degeneration of dopaminergic neurons in the substantia nigra (SN) (Hornykiewicz, 1966). Schizophrenic patients exhibit psychotic symptoms, which may partially result from dysfunction of the mesocortical and hippocampal dopamine (DA) systems (Carlsson and Carlsson, 1990;Jaskiw and Weinberger, 1992). The drugs typically used to treat schizophrenia and Parkinson's disease are D2 antagonists or agonists, respectively, suggesting that the D2 receptor plays an important role in these two neuropsychiatric diseases.Two isoforms of the D2 receptor [the long form (D2L) and the short form (D2S)] have been identified (Bunzow et al., 1988;Dal Toso et al., 1989;Giros et al., 1989;Monsma et al., 1989;Chio et al., 1990;Mack et al., 1991). The D2L and D2S receptors are generated from the same gene by alternative splicing. The D2L receptor has a 29 amino acid insertion in the third cytoplasmic loop of the protein, and this insertion is absent in the D2S receptor. The t...

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Generation Of Dopamine D2l Receptor-deficient Micementioning

confidence: 95%

Section: D2l-deficient Mice Express a Functional D2s Receptormentioning

confidence: 99%

See 2 more Smart Citations

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Wang¹,

Xu²,

et al. 2000

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“…Altogether, 120 drug-resistant colonies were picked up, and the genomic DNA was subjected to Southern blot analysis for confirmation of homologous recombination. The D1R-KO mice were generated using the homologous recombinant ES cells essentially as described previously (Yamaguchi et al, 1996;Koera et al, 1997). The D1R-KO mice were backcrossed to a C57BL/6J (B6/J) strain for 10 generations and maintained in a B6/J genetic background.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D₁Receptor Modulates Hippocampal Representation Plasticity to Spatial Novelty

Tran¹,

Uwano²,

Kimura³

et al. 2008

J. Neurosci.

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The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner, forming relational representations of environmental cues. The importance of glutamatergic systems in learning and in hippocampal neural synaptic plasticity has been shown. However, the role of dopaminergic systems in the response of hippocampal neural plasticity to novel and familiar spatial stimuli remains unclear. To clarify this important issue, we recorded hippocampal neurons from dopamine D 1 receptor knock-out (D1R-KO) mice and their wild-type (WT) littermates under the manipulation of distinct spatial cues in a familiar and a novel environment. Here we report that in WT mice, the majority of place cells quickly responded to the manipulations of distal and proximal cues in both familiar and novel environments. In contrast, the influence of distal cues on spatial firing in D1R-KO mice was abolished. In the D1R-KO mice, the influence of proximal cues was facilitated in a familiar environment, and in a novel environment most of the place cells were less likely to respond to changes of spatial cues. Our results demonstrate that hippocampal neurons in mice can rapidly and flexibly encode information about space from both distal and proximal cues to cipher a novel environment. This ability is necessary for many types of learning, and lacking D1R can radically alter this learning-related neural activity. We propose that D1R is crucially implicated in encoding spatial information in novel environments, and influences the plasticity of hippocampal representations, which is important in spatial learning and memory.

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Distribution of the mRNA encoding the four dopamine D1 receptor subtypes in the brain of the european eel (Anguilla anguilla): Comparative approach to the function of D1 receptors in vertebrates

et al. 2000

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Dopamine 02 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary

Cited by 47 publications

References 44 publications

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Dopamine D₁Receptor Modulates Hippocampal Representation Plasticity to Spatial Novelty

Distribution of the mRNA encoding the four dopamine D1 receptor subtypes in the brain of the european eel (Anguilla anguilla): Comparative approach to the function of D1 receptors in vertebrates

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Dopamine 02 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary

Cited by 47 publications

References 44 publications

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

Dopamine D1Receptor Modulates Hippocampal Representation Plasticity to Spatial Novelty

Distribution of the mRNA encoding the four dopamine D1 receptor subtypes in the brain of the european eel (Anguilla anguilla): Comparative approach to the function of D1 receptors in vertebrates

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Dopamine D₁Receptor Modulates Hippocampal Representation Plasticity to Spatial Novelty