Regulation of Dopamine Receptor Function and Expression

Sibley, David R.; Neve, Kim A.

doi:10.1007/978-1-4757-2635-0_13

Cited by 24 publications

(14 citation statements)

References 154 publications

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“…The results of these studies revealed that persistent treatment with quinpirole (10 M), sulpiride (1 M), or quinpirole ϩ sulpiride significantly increased D 2L receptor density (118 Ϯ 6, 149 Ϯ 17, or 129 Ϯ 9%; n ϭ 5) compared with vehicle treatment (100%). These ligand-induced increases in D 2L receptor expression are consistent with our previous report (Vidi et al, 2008a) and work from others (Sibley and Neve, 1997). No significant changes in CB 1 receptor density were observed upon persistent treatment with either of the D 2 receptor ligands alone or the combination (data not shown).…”

Section: Resultssupporting

confidence: 92%

Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers

Przybyla¹,

Watts²

2009

J Pharmacol Exp Ther

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The cannabinoid CB 1 (CB 1 ) and dopamine D 2 (D 2 ) receptors are coexpressed in the basal ganglia, an area of the brain involved in such processes as cognition, motor function, and emotional control. Several lines of evidence suggest that CB 1 and D 2 receptors may oligomerize, providing a unique pharmacology in vitro and in vivo. However, limited information exists on the regulation of CB 1 and D 2 receptor dimers. We used a novel technique, multicolor bimolecular fluorescence complementation (MBiFC) Increasing evidence suggests that G protein-coupled receptors (GPCRs) may function in receptor dimeric or higher order oligomeric complexes (for review, see Milligan, 2008). One set of receptors that has received significant attention relevant to oligomerization is the CB 1 cannabinoid (CB 1 ) receptor and dopamine D 2 (D 2 ) receptor (for review, see Fuxe et al., 2008). It is thought that the cannabinoid system negatively modulates dopamine circuits as activation of the CB 1 receptor leads to an attenuation of dopamine signaling (Laviolette and Grace, 2006). The CB 1 receptor is widely expressed in the central nervous system, with great abundance in the basal ganglia (Herkenham et al., 1991). CB 1 receptors are located on striatal GABAergic neurons (Herkenham et al., 1991), and they are also found on dendrites in both the dorsal striatum and the nucleus accumbens (Pickel et al., 2006). The D 2 receptor exists as two splice variants, D 2S (short) and D 2L (long). The D 2S variant is highly expressed on presynaptic dopaminergic neurons, whereas the D 2L variant is found postsynaptically on dopaminergic neurons throughout the striatum

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Section: Resultssupporting

confidence: 92%

Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers

Przybyla¹,

Watts²

2009

J Pharmacol Exp Ther

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“…3. Dopamine receptors are subjected to a variety of regulatory mechanisms which can either positively or negatively modulate their expression and functional activity (13). The mechanisms underlying the different forms of dopamine receptor regulation have not yet been completely elucidated.…”

Section: Functional Characteristics Of Dopamine Receptorsmentioning

confidence: 99%

“…Several studies on dopamine receptors have demonstrated that the D 1 receptor displays a comparable mechanism of desensitization, although some difference exists from the classical scheme. In contrast, the regulation of D 2 receptors seems extremely complex with receptor activation variably resulting in functional desensitization, sensitization, up-or down-regulation (13). The regulation of D 2 receptors seems to be influenced by the type and concentration of the agonist or antagonist, the receptor isoform and the cell system.…”

Section: Functional Characteristics Of Dopamine Receptorsmentioning

confidence: 99%

Novel insights in dopamine receptor physiology

Pivonello¹,

Ferone

Lombardi³

et al. 2007

eur j endocrinol

127

103

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The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts its functions via five different receptors, named D 1 -D 5 , belonging to the category of G protein coupled membrane receptors. Dopamine receptors are heterogeneously expressed in different cells, tissues and organs, where they stimulate or inhibit different functions, including neurotransmission and hormone synthesis and secretion. In particular, the dopamineric system has a pivotal role in the physiological regulation of the hypothalamus-pituitary-adrenal axis. Recent data have demonstrated the expression and function of dopamine receptors not only in endocrine organs but also in endocrine tumors, mainly those belonging to the hypothalamus-pituitary-adrenal axis, and also in the so-called 'neuroendocrine' tumors. These data confirm the important role of the dopaminergic system in this endocrine axis, as well as in the neuroendocrine system. This review summarizes the main structural and functional characteristics of dopamine receptors, emphasizing the most recent novelties, and focused on the physiological and pathological regulation of the hypothalamus-pituitary-adrenal axis by the dopaminergic system. In addition, the recent findings on the relationship between dopamine receptors and neuroendocrine tumors are summarized.European Journal of Endocrinology 156 S13-S21

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“…Desensitization and internalization of the dopamine D2 receptor have been described in a variety of cell lines and tissue preparations (Barton et al, 1991;Zhang et al, 1994;Boundy et al, 1995;Ng et al, 1997;Sibley and Neve, 1997;Vickery and von Zastrow, 1999;Kim et al, 2001Kim et al, , 2004. The interaction of arrestins and the dopamine D2 receptor and the contribution of this interaction to receptor internalization have also been investigated but chiefly in studies using heterologous expression of arrestins, GRKs, and the D2 receptor in non-neuronal cells.…”

mentioning

confidence: 99%

Preferential Interaction between the Dopamine D2 Receptor and Arrestin2 in Neostriatal Neurons

Macey

Gurevich

Neve³

2004

Mol Pharmacol

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Dopamine D2 receptor interactions with arrestins and arrestindependent internalization have been characterized using heterologously expressed D2 receptor and arrestins. The purpose of this study was to investigate D2 receptor interaction with endogenous arrestins. Arrestin2 and arrestin3 in striatal homogenates bound to the third cytoplasmic loop of the D2 receptor, and purified arrestin2 and arrestin3 bound to the second and third loops and C terminus of the D2 receptor, in a glutathione S-transferase pull-down assay. In NS20Y neuroblastoma cells expressing an enhanced green-fluorescent protein-tagged D2 receptor (D2-EGFP), 2-h D2 agonist stimulation enhanced the colocalization of D2-EGFP with endogenous arrestin2 and arrestin3. These results suggest that the D2 receptor has the intrinsic ability to bind both nonvisual arrestins.Agonist treatment of D2-EGFP NS20Y cells induced D2 receptor internalization (36 -46%) that was maximal within 20 min, but that was prevented by small interfering RNA-induced depletion of arrestin2 and arrestin3. In neostriatal neurons, 2-h agonist treatment selectively increased the colocalization of the endogenous D2 receptor with arrestin2, whereas receptor colocalization with arrestin3 was reduced. Agonist stimulation caused translocation of arrestin2, but not arrestin3, to the membrane in neurons and selectively enhanced the coimmunoprecipitation of the D2 receptor and arrestin2. All three measures of receptor/arrestin interaction (colocalization, translocation, and coprecipitation) demonstrated selective agonist-induced interaction between the D2 receptor and arrestin2 in neurons.Receptor desensitization is a phenomenon in which receptor responsiveness decreases after continued or repeated stimulation with an agonist. After termination of agonist stimulation, desensitization is followed by resensitization, the reinstatement of the ability to respond to ligands (Krupnick and Benovic, 1998). For G protein-coupled receptors (GPCRs), trafficking of the receptor through various subcellular compartments is an important part of desensitization and resensitization. A model of GPCR desensitization, best characterized for the ␤ 2 -adrenergic receptor, has been developed in which the agonist-activated GPCR is phosphorylated by GPCR kinases (GRKs) or second-messenger-dependent kinases such as protein kinase A (Krupnick and Benovic, 1998). Phosphorylation by GRKs enhances the interaction of the GPCR with additional proteins, termed arrestins. Binding of arrestin causes rapid desensitization of the receptor by inhibiting receptor binding to G proteins and also targets the receptor to clathrin-coated pits for internalization and either degradation or resensitization (Pippig et al., 1995;Tsao et al., 2001). Arrestin can also act as a scaffolding protein, promoting the stable association of signaling proteins with the receptor (Luttrell et al., 2001).The rate of GPCR resensitization depends on the stability of the receptor/arrestin complex. Receptors that dissociate from arrestin near the...

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Regulation of Dopamine Receptor Function and Expression

Cited by 24 publications

References 154 publications

Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers

Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers

Novel insights in dopamine receptor physiology

Preferential Interaction between the Dopamine D2 Receptor and Arrestin2 in Neostriatal Neurons

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Regulation of Dopamine Receptor Function and Expression

Cited by 24 publications

References 154 publications

Ligand-Induced Regulation and Localization of Cannabinoid CB1 and Dopamine D2L Receptor Heterodimers

Ligand-Induced Regulation and Localization of Cannabinoid CB1 and Dopamine D2L Receptor Heterodimers

Novel insights in dopamine receptor physiology

Preferential Interaction between the Dopamine D2 Receptor and Arrestin2 in Neostriatal Neurons

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Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers

Ligand-Induced Regulation and Localization of Cannabinoid CB₁ and Dopamine D_2L Receptor Heterodimers