Isoform-specific uncoupling of the D2 dopamine receptors subtypes

Kendall, Ryan T.; Senogles, Susan E.

doi:10.1016/j.neuropharm.2010.09.018

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…The ICL3 is the only region of difference between D 2L R and D 2S R, and there is evidence that it results in differences in the G protein coupling and signaling capabilities of each D 2 R isoform (Kendall and Senogles, 2011). Recently, it was proposed that the ICL3 of D 2L R, but not the D 2S R, could form a complex with the D 1 R (Pei et al, 2010), but the findings were based on the use of glutathione S-transferase and transactivator of transcription-fused D 2 R ICL3 fragments, which may not accurately mimic native receptor conformations and interactions.…”

Section: Discussionmentioning

confidence: 99%

D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

et al. 2013

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The D 1 dopamine receptor (D 1 R) has been proposed to form a hetero-oligomer with the D 2 dopamine receptor (D 2 R), which in turn results in a complex that couples to phospholipase Cmediated intracellular calcium release. We have sought to elucidate the pharmacology and mechanism of action of this putative signaling pathway. Dopamine dose-response curves assaying intracellular calcium mobilization in cells heterologously expressing the D 1 and D 2 subtypes, either alone or in combination, and using subtype selective ligands revealed that concurrent stimulation is required for coupling. Surprisingly, characterization of a putative D 1 -D 2 heteromer-selective ligand, 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol (SKF83959), found no stimulation of calcium release, but it did find a broad range of cross-reactivity with other G protein-coupled receptors. In contrast, SKF83959 appeared to be an antagonist of calcium mobilization. Overexpression of G qa with the D 1 and D 2 dopamine receptors enhanced the dopamine-stimulated calcium response. However, this was also observed in cells expressing G qa with only the D 1 R. Inactivation of G i or G s with pertussis or cholera toxin, respectively, largely, but not entirely, reduced the calcium response in D 1 R and D 2 R cotransfected cells. Moreover, sequestration of G bg subunits through overexpression of G protein receptor kinase 2 mutants either completely or largely eliminated dopamine-stimulated calcium mobilization. Our data suggest that the mechanism of D 1 R/D 2 R-mediated calcium signaling involves more than receptor-mediated G q protein activation, may largely involve downstream signaling pathways, and may not be completely heteromer-specific. In addition, SKF83959 may not exhibit selective activation of D 1 -D 2 heteromers, and its significant cross-reactivity to other receptors warrants careful interpretation of its use in vivo.

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Section: Discussionmentioning

confidence: 99%

D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

et al. 2013

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“…One mechanism may be that in hypothyroid hamsters there is a difference in dopamine D2 receptor expression in presynaptic and postsynaptic sites. One approach to evaluate this possibility is to investigate the D2 isoforms using RT-PCR method (Kendall and Senogles, 2011). Dopamine D2 receptors are expressed in 2 isoforms: D2short (D2S) and D2long (D2L).…”

Section: 0 Discussionmentioning

confidence: 99%

Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression

Schlenker

Rio

Schultz

2014

Respiratory Physiology & Neurobiology

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Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters.

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“…Each one might preferentially activate alternative downstream signalling pathways. So far, our understanding of this key aspect of GPCR biology has been limited to studies of a few isoforms in unnatural settings 8,9 .…”

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confidence: 99%

Isoforms of GPCR proteins combine for diverse signalling

Snyder¹,

Rajagopal²

2020

Nature

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Isoform-specific uncoupling of the D2 dopamine receptors subtypes

Cited by 6 publications

References 38 publications

D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression

Isoforms of GPCR proteins combine for diverse signalling

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Isoform-specific uncoupling of the D2 dopamine receptors subtypes

Cited by 6 publications

References 38 publications

D1-D2Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

D1-D2Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression

Isoforms of GPCR proteins combine for diverse signalling

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D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

D₁-D₂Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms