Presynaptic Nicotinic Cholinergic Receptors Labeled by [<sup>3</sup>H]Acetylcholine on Catecholamine and Serotonin Axons in Brain

Schwartz, Rochelle D.; Lehmann, John; Kellar, Kenneth J.

doi:10.1111/j.1471-4159.1984.tb02818.x

Cited by 225 publications

(92 citation statements)

References 18 publications

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“…In a more recent study, these workers have demonstrated autoradiographically that 3H-ACh and 3H-nicotine have almost identical binding patterns on rat brain sections (Clarke et al, 1985a). Similarly, the regional distribution of 3H-nicotine binding sites in rat brain found in this study was in good agreement with both the distribution of membrane-bound nicotine binding sites determined by other workers (Marks and Collins, 1982;Yamada et al, 1985) and with the distribution of membrane-bound 3H-ACh binding sites (Schwartz et al, 1982). Furthermore, the agonist binding site of chicken brain and optic lobe, defined by its high affinity for binding 3H-ACh (Schneider et al, 1985) also has essentially identical pharmacology to the neuronal AChR described here.…”

Section: Discussionsupporting

confidence: 81%

“…In general, the affinities of various cholinergic ligands for the neuronal AChRs are in excellent agreement with the values obtained by other workers for binding to intact brain membranes (Clarke et al, 1984;Marks and Collins, 1982;Roman0 and Goldstein, 1980;Yamada et al, 1985). The data are also in good agreement with values obtained by Schwartz et al (1982), who determined the inhibition of 3H-ACh to rodent brain membranes by cholinergic ligands. In a more recent study, these workers have demonstrated autoradiographically that 3H-ACh and 3H-nicotine have almost identical binding patterns on rat brain sections (Clarke et al, 1985a).…”

Section: Discussionsupporting

confidence: 80%

“…Neuronal AChRs have also been investigated using the radiolabeled cholinergic ligands 3H-nicotine (Abood et al, 1980;Clarke et al, 1984;Larsson and Nordberg, 1985;Marks and Collins, 1982;Roman0 and Goldstein, 1980;Yamada et al, 1985) and 3H-ACh (Reulecke and Hucho, 1985;Schneider et al, 1985;Schwartz et al, 1982). The binding of these ligands to rodent brain membrane preparations was of high affinity and inhibited poorly, if at all, by otBGT.…”

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confidence: 99%

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Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Whiting¹,

Lindstrom²

1986

J. Neurosci.

125

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Recently we immunoaffinity-purified an ACh receptor from chicken brain using a monoclonal antibody raised against receptors from fish electric organ (Whiting and Lindstrom, 1986). This neuronal receptor could be affinity-labeled with 3H-bromoacetylcholine, and antisera to it specifically blocked ACh-induced depolarization of chicken ciliary ganglion cells. Here we show that this neuronal ACh receptor binds 3H- nicotine with high affinity (KD = 6.61 +/- 0.13 nM). 3H-Nicotine binding was blocked by various nicotinic cholinergic ligands but not by alpha-bungarotoxin or the muscarinic antagonist atropine. Binding was also blocked by affinity labeling the receptor with bromoacetylcholine (after reduction by dithiothreitol). Additionally, we were able to use rat antisera raised against the chicken brain receptor to isolate a component from detergent extracts of rat brain that also bound 3H- nicotine with high affinity (KD = 1.5 nM). The pharmacology of this putative ACh receptor from rat brain was almost identical to the receptor from chicken brain, and its regional distribution was in good agreement with that of 3H-nicotine binding to rodent brain membranes reported by other workers. Thus, by analogy to the receptor we have purified and characterized from chicken brain, this nicotine-binding component from rat brain is probably a functional mammalian neuronal nicotinic ACh receptor.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 80%

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confidence: 99%

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Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Whiting¹,

Lindstrom²

1986

J. Neurosci.

125

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“…Nigrostriatal damage decreases high affinity nicotine binding sites that are thought to represent α4β2* nAChRs, while α7 nAChRs are unaffected [106,107]. Nigrostriatal damage also leads to dramatic declines in binding of 125 I-α-conotoxinMII [108], a ligand that identifies α6β2* in rodent striatum [80,109].…”

Section: Rodentsmentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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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...

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“…Histochemical and ion flux measurements with synaptosomes have indicated that nAChRs are expressed on DA axon terminals in the striatum (Schwartz et al, 1984;Hill et al, 1993;Colquhoun and Patrick, 1997;Wonnacott, 1997;Jones et al, 2001). Electron microscopy applied with immunolabeling for tyrosine hydroxylase and for the nAChR ␤2 subunit revealed that striatal DA axonal boutons and midbrain DA cell bodies express ␤2* nAChRs (Jones et al, 2001).…”

Section: Nicotinic Receptors In the Mesolimbic Dopamine System And Stmentioning

confidence: 99%

Cholinergic interneuron characteristics and nicotinic properties in the striatum

2002

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ABSTRACT:The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

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Presynaptic Nicotinic Cholinergic Receptors Labeled by [³H]Acetylcholine on Catecholamine and Serotonin Axons in Brain

Cited by 225 publications

References 18 publications

Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Nicotinic receptors as CNS targets for Parkinson's disease

Cholinergic interneuron characteristics and nicotinic properties in the striatum

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Presynaptic Nicotinic Cholinergic Receptors Labeled by [3H]Acetylcholine on Catecholamine and Serotonin Axons in Brain

Cited by 225 publications

References 18 publications

Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Pharmacological properties of immuno-isolated neuronal nicotinic receptors

Nicotinic receptors as CNS targets for Parkinson's disease

Cholinergic interneuron characteristics and nicotinic properties in the striatum

Contact Info

Product

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Presynaptic Nicotinic Cholinergic Receptors Labeled by [³H]Acetylcholine on Catecholamine and Serotonin Axons in Brain