Characterization of the human dopamine D3 receptor expressed in transfected cell lines

MacKenzie, Robert G.; VanLeeuwen, Donald; Pugsley, Thomas A.; Shih, Yu-Hsin; Demattos, S. B.; Tang, Lei; Todd, Richard D.; O’Malley, Karen L.

doi:10.1016/0922-4106(94)90212-7

Cited by 108 publications

(61 citation statements)

References 12 publications

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“…Interestingly, activation of PLC pathway has also been shown to mediate the D 2 -like receptor-induced inhibition of calcium current in striatal neurons (Herná ndez-Lopez et al, 2000). Thus, our results are consistent with the notion that D 2 -like DA receptors can activate the PLC pathway (Vallar et al, 1990;MacKenzie et al, 1994), and through this pathway, they modulate a variety of membrane conductances, including the nonselective cation current described in the present study.…”

Section: Mechanism Of Dopamine Excitation Of Serotonin Neurons 383supporting

confidence: 93%

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D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

Aman¹,

Shen²,

Haj‐Dahmane³

2006

J Pharmacol Exp Ther

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The dorsal raphe (DR) receives a prominent dopamine (DA) input that has been suggested to play a key role in the regulation of central serotoninergic transmission. DA is known to directly depolarize DR serotonin neurons, but the underlying mechanisms are not well understood. Here, we show that activation of D 2 -like dopamine receptors on DR 5-HT neurons elicits a membrane depolarization and an inward current associated with an increase in membrane conductance. The DAinduced inward current (I DA ) exhibits a linear I-V relationship and reverses polarity at around Ϫ15 mV, suggesting the involvement of a mixed cationic conductance. Consistent with this notion, lowering the extracellular concentration of sodium reduces the amplitude of I DA and induces a negative shift of its reversal potential to approximately Ϫ45 mV. This current is abolished by inhibiting G-protein function with GDP␤S. Examination of the downstream signaling mechanisms reveals that activation of the nonselective cation current requires the stimulation of phospholipase C but not an increase in intracellular calcium. Thus, pharmacological inhibition of phospholipase C reduces the amplitude of I DA . In contrast, buffering intracellular calcium has no effect on the amplitude of I DA . Bath application of transient receptor potential (TRP) channels blockers, 2-aminoethoxydiphenyl borate and SKF96365 [1-(␤-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole], strongly inhibits I DA amplitude, suggesting the involvement of TRP-like conductance. These results reveal previously unsuspected mechanism by which D 2 -like DA receptors induce membrane depolarization and enhance the excitability of DR 5-HT neurons.

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Section: Mechanism Of Dopamine Excitation Of Serotonin Neurons 383supporting

confidence: 93%

“…Several reports have provided evidence that D 2 -like DA receptors can also activate PLC and increase the hydrolysis of phosphatidylinositol-4,5 biphosphate (Vallar et al, 1990;MacKenzie et al, 1994). Thus, we investigated whether pharmacological inhibition of PLC/phosphatidylinositol-4,5 biphosphate pathway could affect I DA .…”

Section: Resultsmentioning

confidence: 95%

D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

Aman¹,

Shen²,

Haj‐Dahmane³

2006

J Pharmacol Exp Ther

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“…As a result there is a wide range of values for the affinity of dopamine at the D 2 High site (the high-affinity state of this receptor), 2 nM 19 to 75 nM. 20 One reason for the wide range of dopamine affinities at the D 2 High site is that experiments use different levels of NaCl in the buffer. High levels of NaCl convert D 2 High receptors into their D 2 Low state, especially at 37°C, 21 obscuring the dissociation constant of dopamine at D 2 High, and increasing the error in the computer-assisted resolution of the dissociation constant at the high-affinity state.…”

Section: Affinity Determinationsmentioning

confidence: 99%

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

2002

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“…1993;MacKenzie et al 1994). Most agonists bind to the D3 receptor with higher affinity than to the D2 receptor.…”

Section: The D2 Receptor Subfamilymentioning

confidence: 99%

Molecular Characteristics of Mammalian Dopamine Receptors

Lachowicz

Sibley

1997

Pharmacology & Toxicology

115

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Ahsrmrr; Abstract: Dopamine receptors belong to a large super-gene family of receptors which are linked to their signal transduction pathways through heterotrimeric G proteins. A variety of signalling events are known to be regulated by dopamine receptors including adenylate cyclase and phospholipase activities and various ion channels. Prior to the advent of molecular cloning technology, dopamine receptors were believed to belong to two subtypes, D, and Dz. This distinction was based on both pharmacological and functional criteria. We now know that at least five different dopamine receptors exist although they can still be described as to belonging within "D," and "D2" subfamilies. The D, subfamily consists of two receptors -the D , and D5, whereas the D2, D3 and D4 receptors comprise the D2 subfamily. The cloning and molecular characteristics of these five receptors are described in this review.The discovery of the neurotransmitter dopamine initiated a tremendous multi-disciplinary effort to elucidate its function, regulation and relevance to disease states. Dopamine is known to exert its actions through the binding and activation of specific cell surface receptors which are characteristic of the G-protein coupled receptor family. Before it was established that multiple subtypes of dopamine receptors exist, the stimulatory effect of dopamine on adenylate cyclase activity in the neostriatum was demonstrated (Kebabian & Greengard 1971). Subsequent testing of dopaminergic agonists revealed that some promoted inhibition rather than stimulation of adenylate cyclase in the striatum (Stoof & Kebabian 1981). This discrepancy led to the classification of D I receptors as those which stimulate adenylate cyclase activity and raise intracellular levels of CAMP and D2 receptors as those which inhibit adenylate cyclase activity (reviewed in Kebabian & Calne 1979). In addition to regulating adenylate cyclase, many other intracellular effects have now been ascribed to dopamine receptor stimulation (Huff 1996).Through the application of molecular biological techniques, we now know that there are D, and D? subfamilies of receptors rather than singular receptor subtypes. The D, dopamine receptor subfamily includes the "classical" DI (also called the D I A ) receptor, as well as the D5 (also known as the DIB) receptor. The D5 receptor differs from the D I receptor in primary amino acid sequence and anatomical distribution, but binds D , receptor-selective agonists and antagonists with similar affinity. The D2 receptor subfamily includes the classical D2 receptor, which is found in a short and long isoform (DZS and DZL), and also the D3 and D4 receptors. These D2-like receptors exhibit a variety of pharmacological, structural and, in some cases, functional similarities. The cloning history and molecular properties of the five mammalian dopamine receptor subtypes will be described in this review. The D, Receptor SubfamilyMolecular cloning techniques precipitated the discovery that there are two distinct dopamine receptor subtypes w...

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Characterization of the human dopamine D3 receptor expressed in transfected cell lines

Cited by 108 publications

References 12 publications

D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

Molecular Characteristics of Mammalian Dopamine Receptors

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Characterization of the human dopamine D3 receptor expressed in transfected cell lines

Cited by 108 publications

References 12 publications

D2-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

D2-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

Molecular Characteristics of Mammalian Dopamine Receptors

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Product

Resources

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D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

D₂-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance