Comparative pharmacology of human dopamine D2-like receptor stable cell lines coupled to calcium flux through Gαqo5

Moreland, Robert B.; Nakane, Masaki; Donnelly‐Roberts, Diana L.; Miller, Loan; Chang, Ruidong; Uchic, Marie E.; Terranova, Marc A.; Gubbins, Earl J.; Helfrich, Rosalind; Namovic, Marian T.; El-Kouhen, Odile F.; Masters, Jeffrey N.; Brioni, Jorge D.

doi:10.1016/j.bcp.2004.05.019

Cited by 38 publications

(30 citation statements)

References 39 publications

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“…This implies that in Schild-type experiments in where the cells are pretreated with a receptor-saturating concentration of antagonist, only the very fast-dissociating ones do not produce a substantial decline of the maximal response. The inhibitory effect of clozapine preincubation on dopaminemediated [Ca 2+ ] i transients have successively been reported by Pauwels et al (2001b), Moreland et al (2004), and Dyhring et al (2010). In all three studies, the low EC 50 of dopamine suggests the existence of a pronounced receptor reserve.…”

Section: Functional Assaysmentioning

confidence: 58%

Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism

Vauquelin

Bostoen

Vanderheyden

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Drug-receptor interactions are traditionally quantified in terms of affinity and efficacy, but there is increasing awareness that the drug-on-receptor residence time also affects clinical performance. While most interest has hitherto been focused on slow-dissociating drugs, D(2) dopamine receptor antagonists show less extrapyramidal side effects but still have excellent antipsychotic activity when they dissociate swiftly. Fast dissociation of clozapine, the prototype of the "atypical antipsychotics", has been evidenced by distinct radioligand binding approaches both on cell membranes and intact cells. The surmountable nature of clozapine in functional assays with fast-emerging responses like calcium transients is confirmatory. Potential advantages and pitfalls of the hitherto used techniques are discussed, and recommendations are given to obtain more precise dissociation rates for such drugs. Surmountable antagonism is necessary to allow sufficient D(2) receptor stimulation by endogenous dopamine in the striatum. Simulations are presented to find out whether this can be achieved during sub-second bursts in dopamine concentration or rather during much slower, activity-related increases thereof. While the antagonist's dissociation rate is important to distinguish between both mechanisms, this becomes much less so when contemplating time intervals between successive drug intakes, i.e., when pharmacokinetic considerations prevail. Attention is also drawn to the divergent residence times of hydrophobic antagonists like haloperidol when comparing radioligand binding data on cell membranes with those on intact cells and clinical data.

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Section: Functional Assaysmentioning

confidence: 58%

Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism

Vauquelin

Bostoen

Vanderheyden

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Taken together, these data suggest that both the MPD-induced trafficking of vesicles out of the membrane-associated fraction and the MPD-induced kinetic up-regulation of VMAT-2 in the remaining membrane-associated vesicles are D2 receptor-mediated. However, it should also be noted that QUIN also has some affinity for D3 receptors (Moreland et al, 2004). Because MPD has no significant binding affinity for DA receptors (Markowitz et al, 2006), these effects are probably due to MPD-induced increases in extracellular DA concentrations caused by DAT blockade rather than to a direct interaction between MPD and D2 receptors.…”

Section: Discussionmentioning

confidence: 99%

Methylphenidate-Induced Increases in Vesicular Dopamine Sequestration and Dopamine Release in the Striatum: The Role of Muscarinic and Dopamine D2 Receptors

Volz

Farnsworth

Rowley

et al. 2008

J Pharmacol Exp Ther

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Methylphenidate (MPD) administration alters the subcellular distribution of vesicular monoamine transporter-2 (VMAT-2)-containing vesicles in rat striatum. This report reveals previously undescribed pharmacological features of MPD by elucidating its receptor-mediated effects on VMAT-2-containing vesicles that cofractionate with synaptosomal membranes after osmotic lysis (referred to herein as membrane-associated vesicles) and on striatal dopamine (DA) release. MPD administration increased DA transport into, and decreased the VMAT-2 immunoreactivity of, the membrane-associated vesicle subcellular fraction. These effects were mimicked by the D2 receptor agonist quinpirole and blocked by the D2 receptor antagonist eticlopride. Both MPD and quinpirole increased vesicular DA content. However, MPD increased, whereas quinpirole decreased, K ϩ -stimulated DA release from striatal suspensions. Like MPD, the muscarinic receptor agonist, oxotremorine, increased K ϩ -stimulated DA release. Both eticlopride and the muscarinic receptor antagonist scopolamine blocked MPD-induced increases in K ϩ -stimulated DA release, whereas the N-methyl-D-aspartate receptor antagonist (Ϫ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) was without effect. This suggests that D2 receptors mediate both the MPD-induced redistribution of vesicles away from synaptosomal membranes and the MPD-induced up-regulation of vesicles remaining at the membrane. This results in a redistribution of DA within the striatum from the cytoplasm into vesicles, leading to increased DA release. However, D2 receptor activation alone is not sufficient to mediate the MPD-induced increases in striatal DA release because muscarinic receptor activation is also required. These novel findings provide insight into the mechanism of action of MPD, regulation of DA sequestration/release, and treatment of disorders affecting DA disposition, including attention-deficit hyperactivity disorder, substance abuse, and Parkinson's disease.The ritalinic acid psychostimulant methylphenidate (MPD) is frequently used to treat attention-deficit hyperactivity disorder. It is well established that MPD prevents the clearance of dopamine (DA) from the synaptic cleft by binding to the neuronal DA transporter (DAT) (Wayment et al., 1999;. In addition, MPD also indirectly affects the vesicular monoamine transporter (VMAT)-2, a protein that sequesters cytoplasmic DA inside the synaptic vesicles of nerve terminals. A single MPD treatment increases DA transport, VMAT-2 immunoreactivity, and binding of the VMAT-2 ligand [ 3 H]dihydrotetrabenazine in cytoplasmic vesicles purified from osmotic lysates of rat striatal synaptosomes (Sandoval et al., 2002(Sandoval et al., , 2003Volz et al., 2007a). These effects on cytoplasmic vesicles are D2 receptor-mediated, because the D2 receptor antagonist eticlopride (ETIC) attenuates or blocks these effects, and the D2 receptor agonist quinpirole (QUIN) mimics the effects of MPD (Sandoval et al., 2002;Truong et al., 2004).In co...

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“…Interestingly, distribution of D 4 receptors in brain areas associated with regulation of emotions and cognition such as prefrontal cortex and mesolimbic areas (Matsumoto et al, 1995;Ariano et al, 1997;Tarazi et al, 1997;Oak et al, 2000) also make them an intriguing candidate to play a role in depressive-like behaviors. However, using selective (Moreland et al, 2004), and the lack of efficacy blocking the effect of quinpirole in FST suggest that D 4 receptors are clearly not involved in the mediation of antidepressant-like activity.…”

Section: Discussionmentioning

confidence: 99%

“…We compared the effects of nomifensine, a dopamine uptake inhibitor (Meiergerd and Schenk, 1994) (Moreland et al, 2004). To further clarify the role of specific dopamine receptors in the antiimmobility effect of quinpirole, we assessed the ability of haloperidol, a nonselective D 2 -like receptor antagonist (K i ¼ 0.3, 3.6 and 1.9 nM for D 2 , D 3 , and D 4 receptors, respectively) (Moreland et al, 2004) (Moreland et al, 2004;Patel et al, 1997) to attenuate the quinpirole-induced antidepressant-like response. Results support a major role for dopamine D 2 receptors, a moderate role for D 3 receptors, and no involvement of D 4 dopamine receptors in antidepressant-like effects in the rat FST.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test

Basso

Gallagher

Bratcher

et al. 2005

Neuropsychopharmacol

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Comparative pharmacology of human dopamine D2-like receptor stable cell lines coupled to calcium flux through Gαqo5

Cited by 38 publications

References 39 publications

Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism

Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism

Methylphenidate-Induced Increases in Vesicular Dopamine Sequestration and Dopamine Release in the Striatum: The Role of Muscarinic and Dopamine D2 Receptors

Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test

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