Human Dopamine D3 and D2L Receptors Couple to Inward Rectifier Potassium Channels in Mammalian Cell Lines

Kuzhikandathil, Eldo V.; Yu, Weifeng; Oxford, Gerry S.

doi:10.1006/mcne.1998.0722

Cited by 105 publications

(91 citation statements)

References 26 publications

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“…S10B,H). Application of the selective D2 agonist quinpirole induced hyperpolarization of the membrane potential in two out of four cells, which is consistent with a D2-mediated modulation of K + channels (Kuzhikandathil et al, 1998;Lavine et al, 2002;Beaulieu and Gainetdinov, 2011).…”

Section: Development Of Sodium Currents Firing Of Action Potentials supporting

confidence: 77%

Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons

et al. 2013

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SUMMARYMedium-sized spiny neurons (MSNs) are the only neostriatum projection neurons, and their degeneration underlies some of the clinical features of Huntington's disease. Using knowledge of human developmental biology and exposure to key neurodevelopmental molecules, human pluripotent stem (hPS) cells were induced to differentiate into MSNs. In a feeder-free adherent culture, ventral telencephalic specification is induced by BMP/TGF inhibition and subsequent SHH/DKK1 treatment. + MSNs. Similar to mature MSNs, these neurons carry dopamine and A2a receptors, elicit a typical firing pattern and show inhibitory postsynaptic currents, as well as dopamine neuromodulation and synaptic integration ability in vivo. When transplanted into the striatum of quinolinic acid-lesioned rats, hPS-derived neurons survive and differentiate into DARPP-32 + neurons, leading to a restoration of apomorphine-induced rotation behavior. In summary, hPS cells can be efficiently driven to acquire a functional striatal fate using an ontogeny-recapitulating stepwise method that represents a platform for in vitro human developmental neurobiology studies and drug screening approaches.

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Section: Development Of Sodium Currents Firing Of Action Potentials supporting

confidence: 77%

Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons

et al. 2013

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“…In neurons, dopamine hyperpolarizes the cell membrane and induces inward rectifier potassium current in voltage-clamp mode, an effect mimicked by the D2 receptor agonist quinpirole (30). Human dopamine D3 and D2L receptors activate G-protein-coupled inward rectifier potassium channels (GIRKs) in mammalian cells (31) and, specifically, dopamine receptor 2 forms stable complexes with Kir3 channels (32). Several GIRK isoforms have been found in human pancreatic islets (33).…”

Section: Discussionmentioning

confidence: 99%

Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion

Rubı́

Ljubicic

Pournourmohammadi

et al. 2005

Journal of Biological Chemistry

225

205

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Dopamine is a neurotransmitter that plays a critical role in neurological and psychiatric disorders, such as schizophrenia, Parkinson disease, and drug addiction (1). Increasing evidence also shows implication of dopamine in various physiological functions such as cell proliferation (2), gastrointestinal protection (3), and inhibition of prolactin secretion (4). Effects of dopamine on insulin secretion in general and on pancreatic beta cell function in particular have been poorly studied. Insulin exocytosis from the beta cell is primarily controlled by metabolismsecretion coupling. First, glucose equilibrates across the plasma membrane and is phosphorylated by glucokinase, initiating glycolysis (5). Subsequently, mitochondrial metabolism generates ATP, which promotes the closure of ATP-sensitive potassium channels and, as a consequence, depolarization of the plasma membrane (6). This leads to calcium influx through voltage-gated calcium channels and a rise in cytosolic calcium, triggering insulin exocytosis (6, 7). Additional signals participating in the amplifying pathway (8) are necessary to reproduce the sustained secretion elicited by glucose. Insulin secretion evoked by glucose metabolism can be further modulated by parasympathetic and sympathetic neurotransmitters (9).Treatment with dopamine precursor L-dopa in humans suffering from Parkinson disease reduces insulin secretion upon oral glucose tolerance test (10). In rodents, a single injection with L-dopa results in the accumulation of dopamine in beta cells and inhibition of the insulin secretory responses (11,12). In isolated islets, analogues of dopamine inhibit glucose-stimulated insulin release (13), whereas one study reports potentiation of insulin secretion upon acute dopamine accumulation (14). Taken as a whole, these previous studies suggest that beta cells might be directly responsive to dopamine. Here, we investigated the molecular mechanisms implicated in beta cell responses to dopamine action. In particular, the present data demonstrate the presence of dopamine receptors in beta cells. Moreover, the inhibitory effects of dopamine are predominantly ascribed to activation of the D2-like receptor family members. MATERIALS AND METHODS INS-1E Cells and Pancreatic Islets-INS-1Ecells, used as a well differentiated beta cell clone (15), were cultured in a humidified atmosphere containing 5% CO 2 in a medium composed of RPMI 1640 supplemented with 10 mM Hepes, 5% (v/v) heat-inactivated fetal calf serum, 2 mM glutamine, 100 units/ml penicillin, 100 g/ml streptomycin, 1 mM sodium pyruvate, and 50 M 2-mercaptoethanol. For rodent islets, Wistar rats or BALB/c mice weighing 200 -250 g and 25-30 g, respectively, were obtained from in-house breeding (CMU-Zootechnie, Geneva, Switzerland). We followed the principles of laboratory animal care, and the study was approved by the responsible ethics committee. Pancreatic islets were isolated by collagenase digestion and handpicking from male Wistar rats or BALB/c mice as described previously (16). Isolated islets w...

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“…Reserpine reduced and nomifensine increased DA levels. Quinpirole inhibits the D 2 autoreceptor (Kuzhikandathil et al, 1998) and, by DIV20, inhibits DA levels. The effects of nomifensine were enhanced by reserpine and by sulpiride, an antagonist for D 2 receptor.…”

Section: Maturation Of Da Neurons In Vitromentioning

confidence: 99%

A Specific Survival Response in Dopamine Neurons at Most Risk in Parkinson's Disease

Murase¹,

McKay²

2006

J. Neurosci.

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Human Dopamine D3 and D2L Receptors Couple to Inward Rectifier Potassium Channels in Mammalian Cell Lines

Cited by 105 publications

References 26 publications

Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons

Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons

Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion

A Specific Survival Response in Dopamine Neurons at Most Risk in Parkinson's Disease

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