Differential Alterations in Nicotinic Receptor α6 and β3 Subunit messenger RNAs in Monkey Substantia nigra After Nigrostriatal Degeneration

Quik, Maryka; Polonskaya, Yelena; Gillespie, Alison; Lloyd, G. Kenneth; Langston, J. William

doi:10.1016/s0306-4522(00)00244-x

Cited by 40 publications

(37 citation statements)

References 59 publications

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“…Studies to evaluate effects of nigrostriatal damage on striatal ␣7 nAChRs are difficult because of their low expression levels in rat, monkey, and human striatum. However, where such studies have been done, ␣7 receptor expression seems not to change with lesioning (Quik et al, 2000a(Quik et al, , 2003. These findings are consistent with the concept that ␣7 nAChRs are present on nondopaminergic terminals, including notably glutamatergic afferents, in the striatum (Fig.…”

Section: B Effect Of Nigrostriatal Damagesupporting

confidence: 85%

“…The molecular basis for the differential regulation of various striatal nAChR subtypes is an area actively under investigation, the ␣4␤2* nAChR subtype being most extensively investigated to date (Govind et al, 2009; Marks et al, 1983;Schwartz and Kellar, 1983;Benwell et al, 1988;Perry et al, 1999;McCallum et al, 2006;Staley et al, 2006;Xiao et al, 2009;Moretti et al, 2010 ␣4␣5␤2 No change Rats Moretti et al, 2010 ␣7 1or No change Rats, mice, monkeys Pauly et al, 1991;Quik et al, 2000a;Lai et al, 2005;Moretti et al, 2010 ␣6␤2* AND ␣4␤2* NACHRS: DRUG TARGETS FOR PARKINSON'S DISEASEal., 2009). There is a consensus that up-regulation of ␣4␤2* nAChRs is primarily controlled at the post-transcriptional level, with little change in ␣4 or ␤2 nAChR mRNA levels (Marks et al, 1992).…”

Section: A Effect Of Long-term Nicotine Administrationmentioning

confidence: 99%

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α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Quik

Wonnacott²

2011

Pharmacol Rev

177

185

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Section: B Effect Of Nigrostriatal Damagesupporting

confidence: 85%

Section: A Effect Of Long-term Nicotine Administrationmentioning

confidence: 99%

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Quik

Wonnacott²

2011

Pharmacol Rev

177

185

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“…Recent work using oocytes that expressed complex nAChRs composed of multiple ␣ and ␤ subunits, including ␣6, indicates that ␣-conotoxin MII may also bind to nAChRs that contain an ␣6 subunit (Vailati et al, 1999;Kuryatov et al, 2000). Because ␣6 mRNA is prominently present in monkey substantia nigra (Quik et al, 2000a;Quik et al, 2000b;Han et al, 2000) and ␣3 mRNA is present in much lower abundance, if at all (Cimino et al, 1992;Han et al, 2000), these results may suggest that the primary presynaptic nicotinic receptor population is one that contains the ␣6 nicotinic receptor subunit. The ␤ subunit present in combination with the ␣6 subunit in ␣-conotoxin MII-sensitive nAChRs is also under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Starting 2.5 weeks after treatment, locomotor activity was again measured for a 10-day period. The severity of the parkinsonian syndrome after MPTP treatment was rated using a modified monkey parkinsonian rating scale (Langston et al, 2000;Quik et al, 2000b). Five clinical parameters were evaluated including spatial hypokinesia, body bradykinesia, manual dexterity, balance, and freezing; each of which has a 5-point range with 0 being normal and 4 being severely affected, allowing for a composite score ranging between 0 (normal) to 20 (severely parkinsonian).…”

Section: Methodsmentioning

confidence: 99%

“…Binding was conducted as described previously (Quik et al, 2000b). Briefly, 20-m-thick monkey tissue sections were thawed and incubated with or without competing ligand at room temperature for 40 min in buffer (50 mM Tris, pH 7.0, 120 mM NaCl, 5 mM KCl, 2.5 mM CaCl 2 , and 1.0 mM MgCl 2 ) plus 125 I-epibatidine (2200 Ci/mmol; PerkinElmer Life Sciences).…”

Section: Methodsmentioning

confidence: 99%

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Loss of Nicotinic Receptors in Monkey Striatum after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment Is Due to a Decline in α-Conotoxin MII Sites

Kulak

McIntosh²,

Quik

2002

Mol Pharmacol

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Nicotinic acetylcholine receptors (nAChRs) in the basal ganglia are a potential target for new therapeutics for Parkinson's disease. As an approach to detect expression of nAChRs in monkeys, we used 125 I-epibatidine, an agonist at nAChRs containing ␣2 to ␣6 subunits. 125I-Epibatidine binding sites are expressed throughout the control monkey brain, including the basal ganglia. The ␣3/␣6-selective antagonist ␣-conotoxin MII maximally inhibited 50% of binding in the caudate-putamen and had no effect on 125 I-epibatidine binding in the frontal cortex or thalamus. In contrast, inhibition experiments with nicotine, cytisine, and 3-(2(S)-azetidinylmethoxy)pyridine⅐2HCl (A85380) showed a complete block of 125 I-epibatidine binding in all regions investigated and did not discriminate between the ␣-conotoxin MII-sensitive and -insensitive populations in the striatum. To assess the effects of nigrostriatal damage, monkeys were rendered parkinsonian with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals with moderate striatal damage (dopamine transporter levels ϳ30% of control) had a 40 to 50% decrease in 125 I-epibatidine binding. Inhibition studies showed that the decrease in epibatidine binding was due to loss of ␣-conotoxin MII-sensitive nAChRs. Monkeys with severe nigrostriatal damage (dopamine transporter levels Յ5% of control) exhibited a 55 to 60% decrease in 125 I-epibatidine binding, which seemed to be due to a complete loss of ␣-conotoxin MII nAChRs and a partial loss of other nAChR subtypes. These results show that nAChRs expressed in the primate striatum have similar affinities for nicotine, cytisine, and A85380, that ␣-conotoxin MII discriminates between nAChR populations in the caudate and putamen, and that ␣-conotoxin MII-sensitive nAChRs are selectively decreased after MPTP-induced nigrostriatal damage.Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine neurons in the substantia nigra (Lang and Lozano, 1998). The ensuing dopaminergic deficit results in motor symptoms that are relieved with administration of the dopamine precursor Ldopa. However, motor and other complications develop with long-term use of L-dopa, and furthermore, this drug does not halt disease progression. These observations raise the need for alternative therapeutic approaches. Accumulating evidence suggests that activation of nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for PD. This is based on findings showing 1) an apparent protective effect of tobacco use on PD (Morens et al., 1995;Quik and Jeyarasasingam, 2000), 2) positive effects of nicotine administration on parkinsonian symptomatology in humans (Kelton et al., 2000) and in monkeys (Schneider et al., 1998), and 3) the ability of nicotine to stimulate dopamine release in the caudate-putamen (MacDermott et al., 1999).Multiple nAChR subunits have been identified in the basal ganglia of rodents and nonhuman primates, including ␣2 to ␣7 and ␤2 to ␤4 (Jones et...

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Localization of [³H]nicotine, [³H]cytisine, [³H]epibatidine, and [¹²⁵I]α‐bungarotoxin binding sites in the brain of Macaca mulatta

Han

Zoli

Cardona

et al. 2003

J of Comparative Neurology

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We determined the localization of [(3)H]nicotine, [(3)H]cytisine, [(3)H]epibatidine, and [(125)I]alpha-bungarotoxin binding sites in the brain of rhesus monkey by means of receptor autoradiography. The labelings by [(3)H]nicotine, [(3)H]cytisine, and [(3)H]epibatidine were highly concordant, except for epibatidine. Layer IV of some cortical areas, most thalamic nuclei, and presubiculum displayed high levels of labeling for the three ligands. Moderate levels of binding were detected in the subiculum, the septum, and the mesencephalon. Low levels were present in layers I-II and VI of the cortex, the cornu Ammonis, the dentate gyrus, and the amygdala. In addition, the level of epibatidine labeling was very high in the epithalamic nuclei and the interpeduncular nucleus, whereas labeling by nicotine and cytisine was very weak in the same regions. The distribution of [(125)I]alpha-bungarotoxin binding differed from the binding of the three agonists. The labeling was dense in layer I of most cortical areas, dentate gyrus, stratum lacunosum-moleculare of CA1 field, several thalamic nuclei, and medial habenula. A moderate labeling was found in layers V and VI of the prefrontal and frontal cortices, layer IV of primary visual cortex, amygdala, septum, hypothalamus, and some mesencenphalic nuclei. A weak signal was also detected in subiculum, claustrum, stratum oriens, and stratum lucidum of cornu Ammonis and also in some mesencephalic nuclei. The distribution of nicotine, cytisine, and epibatidine bindings corresponds broadly to the patterns observed in rodents, with the marked exception of the epithalamus. However, in monkey, those distributions match the distribution of alpha2 messenger RNA, rather than that of alpha4 transcripts as it exists in rodent brains. The distribution of the binding sites for alpha-bungarotoxin is larger in the brain of rhesus monkeys than in rodent brain, suggesting a more important role of alpha7 receptors in primates.

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Differential Alterations in Nicotinic Receptor α6 and β3 Subunit messenger RNAs in Monkey Substantia nigra After Nigrostriatal Degeneration

Cited by 40 publications

References 59 publications

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Loss of Nicotinic Receptors in Monkey Striatum after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment Is Due to a Decline in α-Conotoxin MII Sites

Localization of [³H]nicotine, [³H]cytisine, [³H]epibatidine, and [¹²⁵I]α‐bungarotoxin binding sites in the brain of Macaca mulatta

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Differential Alterations in Nicotinic Receptor α6 and β3 Subunit messenger RNAs in Monkey Substantia nigra After Nigrostriatal Degeneration

Cited by 40 publications

References 59 publications

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Loss of Nicotinic Receptors in Monkey Striatum after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment Is Due to a Decline in α-Conotoxin MII Sites

Localization of [3H]nicotine, [3H]cytisine, [3H]epibatidine, and [125I]α‐bungarotoxin binding sites in the brain of Macaca mulatta

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Localization of [³H]nicotine, [³H]cytisine, [³H]epibatidine, and [¹²⁵I]α‐bungarotoxin binding sites in the brain of Macaca mulatta