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

Han, Zhi-Yan; Zoli, Michèle; Cardona, Ana; Bourgeois, Jean-Pierre; Changeux, Jean‐Pierre; Novère, Nicolas Le

doi:10.1002/cne.10659

Cited by 95 publications

(62 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major nAChR receptor populations in cortex seem to contain ␣4␤2 subunits, in agreement with previous studies in rodents (Flores et al, 1992;Zoli et al, 2002;Champtiaux et al, 2003). In contrast, ␣2* nAChRs were also identified in monkey cortex, an observation consistent with the identification of ␣2 mRNA in monkey brain (Han et al, 2003). Both ␣4␤2 and ␣4␤2␣2 nAChRs seem to be present with this latter subtype representing ϳ16% of the ␣4␤2* cortical receptor population.…”

supporting

confidence: 90%

“…In addition, monkeys with nigrostriatal damage exhibit symptoms that resemble those in Parkinson's disease, with the motor deficits reversed by the same drug used to treat this disorder. Studies have shown that the ␣2-␣7 and ␤2-␤4 nAChR transcripts are present in monkey substantia nigra (Han et al, 2000;Quik et al, 2000a,b) and that binding sites for 125 I-epibatidine, [ 3 H]cytisine, 125 I-A85380, 125 I-␣-conotoxin MII, and 125 I-␣-bungarotoxin are expressed in the striatum and substantia nigra (Quik et al, 2001;Kulak et al, 2002a,b;Han et al, 2003). Furthermore, there are differential changes in nAChRs after MPTP treatment, with a complete loss of 125 I-␣-conotoxin MII sites and also declines in ␣-conotoxin MII-resistant 125 Iepibatidine sites.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or l-DOPA

Quik¹,

Vailati²,

Bordia³

et al. 2004

Mol Pharmacol

View full text Add to dashboard Cite

Nicotinic acetylcholine receptors (nAChRs) represent an important modulator of striatal function both under normal conditions and in pathological states such as Parkinson's disease. Because different nAChR subtypes may have unique functions, immunoprecipitation and ligand binding studies were done to identify their subunit composition. As in the rodent, ␣2, ␣4, ␣6, ␤2, and ␤3 nAChR subunit immunoreactivity was identified in monkey striatum. However, distinct from the rodent, the present results also revealed the novel presence of ␣3 nAChR subunit-immunoreactivity in this same region, but not that for ␣5 and ␤4. Relatively high levels of ␣2 and ␣3 subunits were also identified in monkey cortex, in addition to ␣4 and ␤2. Experiments were next done to determine whether striatal subunit expression was changed with nigrostriatal damage. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment decreased ␣6 and ␤3 subunit immunoreactivity by ϳ80% in parallel with the dopamine transporter, suggesting that they are predominantly expressed on nigrostriatal dopaminergic projections. In contrast, ␣3, ␣4, and ␤2 subunit immunoreactivity was decreased ϳ50%, whereas ␣2 was not changed. These data, together with those from dual immunoprecipitation and radioligand binding studies ([ 3 H]cytisine, 125 I-␣-bungarotoxin, and 125 I-␣-conotoxin MII) suggest the following: that ␣6␤2␤3, ␣6␣4␤2␤3, and ␣3␤2* nAChR subtypes are present on dopaminergic terminals and that the ␣4␤2 subtype is localized on both dopaminergic and nondopaminergic neurons, whereas ␣2␤2* and ␣7 receptors are localized on nondopaminergic cells in monkey striatum. Overall, these results suggest that drugs targeting non-␣7 nicotinic receptors may be useful in the treatment of disorders characterized by nigrostriatal dopaminergic damage, such as Parkinson's disease.Parkinson's disease is a neurodegenerative disorder characterized by severe movement disability (Olanow, 2004;Samii et al., 2004). Although the underlying cause seems to be a loss of nigrostriatal dopaminergic neurons, other neurotransmitter systems are also affected. This includes the cholinergic system, in which declines have been observed in several cholinergic measures, including nicotinic acetylcholine receptors (nAChRs ABBREVIATIONS: nAChR, nicotinic acetylcholine receptor; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; A85380, 3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride; RTI-121, 3␤-(4-iodophenyl)tropane-2␤-carboxylic acid isopropyl ester; BSA, bovine serum albumin; CI, confidence interval; *, nicotinic receptors containing the indicated ␣ and/or ␤ subunit and also additional undefined subunits.

show abstract

supporting

confidence: 90%

mentioning

confidence: 99%

Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or l-DOPA

Quik¹,

Vailati²,

Bordia³

et al. 2004

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…nAChR subunit mRNAs in the primate nigrostriatal system include the α2, α4 through α7, and β2 through β4 transcripts [82,83]. Receptor binding studies with 125 I-epibatidine demonstrate that receptors are expressed in both the striatum and substantia nigra [84][85][86]. Subsequent studies with more selective ligands, such as 125 I-α-conotoxinMII indicated the presence of α6β2* nAChR subtypes, in the nigrostriatal system [84,87], while the use of 125 I-epibatidine in the presence of unlabelled α-conotoxinMII suggested the presence of α4β2* receptors.…”

Section: Monkeysmentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

View full text Add to dashboard Cite

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

show abstract

“…21) In rhesus monkeys, nAChRs a7 subtype distributes highest in the thalamus, moderate in the cortex and low in the cerebellum. [22][23][24][25] As shown in Fig. 4, successful images could be obtained.…”

Section: In Vivo Imaging Agents For Nachr A7 Sub-typementioning

confidence: 92%

Central in Vivo Nicotinic Acetylcholine Receptor Imaging Agents for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)

Ogawa

Tsukada

Hatano

et al. 2009

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

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

Cited by 95 publications

References 65 publications

Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or l-DOPA

Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or l-DOPA

Nicotinic receptors as CNS targets for Parkinson's disease

Central in Vivo Nicotinic Acetylcholine Receptor Imaging Agents for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)

Contact Info

Product

Resources

About