Modulation of Dopamine Transporter Activity by Nicotinic Acetylcholine Receptors and Membrane Depolarization in Rat Pheochromocytoma PC12 Cells

Huang, Chuen-Lin; Chen, Hsiao‐Chun; Huang, Nien-Tsu; Yang, De‐Ming; Kao, Lung‐Sen; Chen, Jin‐Chung; Lai, Hsing‐Lin; Chern, Yijuang

doi:10.1046/j.1471-4159.1999.0722437.x

Cited by 18 publications

(15 citation statements)

References 40 publications

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“…In striatum, presynaptic and/or axonal α6 L9′S channels may similarly depolarize DA fibers/terminals due to these changes at the single channel level. Axonal depolarization can significantly alter the action potential waveform (Shu et al, 2006; Kole et al, 2007), and tonic depolarization of the presynaptic terminal would be expected to reduce V max for the DA transporter (Huang et al, 1999), resulting in slower DA re-uptake following release. Indeed, in PC12 cells expressing DAT and nAChRs, nAChR activation resulted in membrane depolarization and a reduction in DAT uptake velocity (Huang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Axonal depolarization can significantly alter the action potential waveform (Shu et al, 2006; Kole et al, 2007), and tonic depolarization of the presynaptic terminal would be expected to reduce V max for the DA transporter (Huang et al, 1999), resulting in slower DA re-uptake following release. Indeed, in PC12 cells expressing DAT and nAChRs, nAChR activation resulted in membrane depolarization and a reduction in DAT uptake velocity (Huang et al, 1999). Although our DAT binding and functional experiments show that there are no intrinsic differences in DAT expression levels or enzymatic function in vitro in the four genotypes examined (Figure 7), they do not address the possibility that α6 L9′S channels depolarize DA fibers and reduce DAT function in slices and/or in vivo .…”

Section: Discussionmentioning

confidence: 99%

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Cholinergic Modulation of Locomotion and Striatal Dopamine Release Is Mediated by 6 4* Nicotinic Acetylcholine Receptors

Drenan

Grady

Steele

et al. 2010

Journal of Neuroscience

117

186

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Dopamine (DA) release in striatum is governed by firing rates of midbrain DA neurons, striatal cholinergic tone, and nicotinic ACh receptors (nAChRs) on DA presynaptic terminals. DA neurons selectively express α6* nAChRs, which show high ACh and nicotine sensitivity. To help identify nAChR subtypes that control DA transmission, we studied transgenic mice expressing hypersensitive α6L9′S* receptors. α6L9′S mice are hyperactive, travel greater distance, exhibit increased ambulatory behaviors such as walking, turning, and rearing, and show decreased pausing, hanging, drinking, and grooming. These effects were mediated by α6α4* pentamers, as α6L9′S mice lacking α4 subunits displayed essentially normal behavior. In α6L9′S mice, receptor numbers are normal, but loss of α4 subunits leads to fewer and less sensitive α6* receptors. Gain-of-function nicotine-stimulated DA release from striatal synaptosomes requires α4 subunits, implicating α6α4β2* nAChRs in α6L9′S mouse behaviors. In brain slices, we applied electrochemical measurements to study control of DA release by α6L9′S nAChRs. Burst stimulation of DA fibers elicited increased DA release relative to single action potentials selectively in α6L9′S, but not WT or α4KO/α6L9′S, mice. Thus, increased nAChR activity, like decreased activity, leads to enhanced extracellular DA release during phasic firing. Bursts may directly enhance DA release from α6L9′S presynaptic terminals, as there was no difference in striatal DA receptor numbers or DA transporter levels or function in vitro. These results implicate α6α4β2* nAChRs in cholinergic control of DA transmission, and strongly suggest that these receptors are candidate drug targets for disorders involving the DA system.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cholinergic Modulation of Locomotion and Striatal Dopamine Release Is Mediated by 6 4* Nicotinic Acetylcholine Receptors

Drenan

Grady

Steele

et al. 2010

Journal of Neuroscience

117

186

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“…SNAP 1.0 m m infusion did not affect dialysate concentrations of DOPAC + HVA (data not shown). Nifedipine is a well known inhibitor of voltage‐sensitive l ‐type Ca 2+ channels (Huang et al . 1999).…”

Section: Snap‐induced Increases In Dialysate Concentrations Of Da + 3mentioning

confidence: 99%

Role of the nitric oxide/cyclic GMP pathway and extracellular environment in the nitric oxide donor‐induced increase in dopamine secretion from PC12 cells: a microdialysis in vitro study

Serra¹,

Rocchitta²,

Delogu³

et al. 2003

Journal of Neurochemistry

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In vitro microdialysis was used to investigate the mechanism of nitric oxide (NO) donor-induced changes in dopamine (DA) secretion from PC12 cells. Infusion of the NO-donor S-nitroso-N-acetylpenicillamine (SNAP, 1.0 mM) induced a long-lasting increase in DA and 3-methoxytyramine (3-MT) dialysate concentrations. SNAP-induced increases were inhibited either by pre-infusion of the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4] oxadiazolo [4,3]quinoxalin-1-one (ODQ, 0.1 mM) or by Ca 2+ omission. Ca 2+ re-introduction restored SNAP effects. SNAP-induced increases in DA + 3-MT were unaffected by co-infusion of the L-type Ca 2+ channel inhibitor nifedipine. The NO-donor (+ / -)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3, 1.0 mM) induced a short-lasting decrease in dialysate DA + 3-MT. Ascorbic acid (0.2 mM) co-infusion allowed NOR-3 to increase dialysate DA + 3-MT. ODQ pre-infusion inhibited NOR-3 + ascorbic acid-induced DA + 3-MT increases. Infusion of high K + (75 mM) induced a 2.5-fold increase in dialysate DA + 3-MT. The increase was abolished by NOR-3 co-infusion. Conversely, co-infusion of ascorbic acid (0.2 mM) with NOR-3 + high K + restored high K + effects. Co-infusion of nifedipine inhibited high K + -induced DA + 3-MT increases. These results suggest that activation of the NO / sGC / cyclic GMP pathway may be the underlying mechanism of extracellular Ca 2+ -dependent effects of exogenous NO on DA secretion from PC12 cells. Extracellular Ca 2+ entry may occur through nifedipine-insensitive channels. NO effects and DA concentrations in dialysates largely depend on both the timing of NO generation and the extracellular environment in which NO is generated.

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“…Surprisingly, nicotine (0.4 mg/kg) has been reported to increase DA clearance (enhance DAT function) in the nucleus accumbens in anesthetized rats (Hart and Ksir, 1996). The latter results also contrast findings in vitro in which nicotine and another nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium, have been reported to decrease [ 3 H]DA uptake into chopped striatum and PC12 cells, respectively (Izenwasser et al, 1991;Huang et al, 1999). However, these in vitro findings have not been replicated (Carr et al, 1989;Kramer et al, 1989;Rowell and Hill 1993;Zhu et al, 2004).…”

mentioning

confidence: 94%

Nicotinic Receptor Modulation of Dopamine Transporter Function in Rat Striatum and Medial Prefrontal Cortex

Middleton

Cass²,

Dwoskin³

2003

J Pharmacol Exp Ther

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Nicotine activates nicotinic acetylcholine receptors (nAChRs) on dopamine (DA) terminals to evoke DA release, which subsequently is taken back up into the terminal via the DA transporter (DAT). nAChRs may modulate DAT function thereby contributing to the regulation of synaptic DA concentrations. The present study determined the dose-response for nicotine (0.1-0.8 mg/kg, s.c.) to modulate DA clearance in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in urethane anesthetized rats and determined if this effect was mediated by nAChRs. Exogenous DA (200 M) was pressureejected at 5-min intervals until reproducible baseline signals were obtained. Subsequently, nicotine or saline was administered, and DA pressure ejection continued at 5-min intervals for 60 min. In both striatum and mPFC, signal amplitude decreased by ϳ20% across the 60-min session in saline-injected rats. A monophasic dose-response curve was found in striatum, with a maximal 50% decrease in signal amplitude after 0.8 mg/kg. In contrast, a U-shaped dose-response curve was found in mPFC, with a maximal 50% decrease in signal amplitude after 0.4 mg/kg. Onset of nicotine response occurred 10 to 15 min after injection in both brain regions; however, the amount of time before maximal response was 45 and 30 min in striatum and mPFC, respectively. Mecamylamine (1.5 mg/kg) completely inhibited the nicotine-induced (0.8 and 0.4 mg/kg) decrease in signal amplitude in striatum and mPFC, respectively, indicating mediation by nAChRs. Thus, nicotine enhances DA clearance in striatum and mPFC in a mecamylamine-sensitive manner, indicating that nAChRs modulate DAT function in these brain regions.Previous research on the neurobiology of reward and drug addiction has focused on the mesocorticolimbic and nigrostriatal dopamine (DA) systems, emphasizing the role of the nucleus accumbens, medial prefrontal cortex (mPFC), and striatum. The accumbens shell, which is innervated by dopaminergic projections from the ventral tegmental area, and its associated neurocircuitry are believed to encode primary appetitive stimuli associated with unconditioned drug reward

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Modulation of Dopamine Transporter Activity by Nicotinic Acetylcholine Receptors and Membrane Depolarization in Rat Pheochromocytoma PC12 Cells

Cited by 18 publications

References 40 publications

Cholinergic Modulation of Locomotion and Striatal Dopamine Release Is Mediated by 6 4* Nicotinic Acetylcholine Receptors

Cholinergic Modulation of Locomotion and Striatal Dopamine Release Is Mediated by 6 4* Nicotinic Acetylcholine Receptors

Role of the nitric oxide/cyclic GMP pathway and extracellular environment in the nitric oxide donor‐induced increase in dopamine secretion from PC12 cells: a microdialysis in vitro study

Nicotinic Receptor Modulation of Dopamine Transporter Function in Rat Striatum and Medial Prefrontal Cortex

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