Differential nicotinic receptor expression in monkey basal ganglia: Effects of nigrostriatal damage

Quik, Maryka; Polonskaya, Yelena; McIntosh, J. Michael; Kulak, Jennifer M.

doi:10.1016/s0306-4522(02)00106-9

Cited by 25 publications

(27 citation statements)

References 59 publications

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“…The proportion of ␣-conotoxinMII-sensitive to insensitive nAChR subtypes is ϳ30:70 in rodents (Cartier et al, 1996;Kulak et al, 1997;Grady et al, 2007) but this ratio is ϳ50:50 in monkey striatum (Kulak et al, 2002). This might reflect the additional presence of ␣-conotoxinMIIsensitive ␣3␤2* nAChR on nigrostriatal terminals in monkey brain .…”

Section: Nicotinic Acetylcholine Receptor Subtypes In the Striatummentioning

confidence: 96%

“…Work in this brain region is much more limited; however, studies in rats and monkeys have shown that nAChR binding is decreased with lesioning Quik et al, 2002Quik et al, , 2010. With respect to subtype selectivity, there is a more pronounced decline in ␣6␤2* compared with ␣4␤2* nAChR expression in the SN pars compacta with nigrostriatal damage (Quik et al, 2002.…”

Section: B Effect Of Nigrostriatal Damagementioning

confidence: 99%

See 1 more Smart Citation

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: Nicotinic Acetylcholine Receptor Subtypes In the Striatummentioning

confidence: 96%

Section: B Effect Of Nigrostriatal Damagementioning

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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“…Rodent striatal DA axon terminals contain b2 subunits coexpressed predominantly with a4, or a6, a5 and also b3 subunits within at least three types of heteromeric pentamers, including a4b2, a6b2b3, and a6a4b2b3 (Champtiaux et al, 2003;Charpantier et al, 1998;Cui et al, 2003;Exley and Cragg, in press;Grady et al, 2002;Klink et al, 2001;Quik and McIntosh, 2006;Quik et al, 2005;Salminen et al, 2004;Zoli et al, 2002). Unlike other subunits, expression of the a6 subunit is relatively restricted to catecholaminergic (and some visual system) neurons (Le Novere et al, 1996;Quik et al, 2001Quik et al, , 2002. Moreover, after somatic expression of a6 mRNA in VTA/SN DA neurons (Azam et al, 2002(Azam et al, , 2007, plasmamembrane a6*-nAChRs on DA axon terminals (Quik et al, 2002;Zoli et al, 2002) may account for up to 40% of b2*-nAChRs (in rat) .…”

Section: Introductionmentioning

confidence: 99%

“…Unlike other subunits, expression of the a6 subunit is relatively restricted to catecholaminergic (and some visual system) neurons (Le Novere et al, 1996;Quik et al, 2001Quik et al, , 2002. Moreover, after somatic expression of a6 mRNA in VTA/SN DA neurons (Azam et al, 2002(Azam et al, , 2007, plasmamembrane a6*-nAChRs on DA axon terminals (Quik et al, 2002;Zoli et al, 2002) may account for up to 40% of b2*-nAChRs (in rat) . Given their restricted localization to striatal DA axons, a6*-nAChRs are attracting attention as promising targets for selective pharmacotherapies in dopaminergic disorders including nicotine addiction and Parkinson's disease (Quik and McIntosh, 2006).…”

Section: Introductionmentioning

confidence: 99%

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

Exley

Clements

Hartung

et al. 2007

Neuropsychopharmacol

227

262

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Modulation of striatal dopamine (DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive effects of nicotine. Nicotine, by desensitizing b2 subunit-containing (b2*) nicotinic acetylcholine receptors (nAChRs) on striatal DA axons, significantly enhances how DA is released by reward-related burst activity compared to nonreward-related tonic activity. This action provides a synaptic mechanism for nicotine to facilitate the DA-dependent reinforcement. The subfamily of b2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of a6b2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real-time using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in mouse striatal slices. The a6-specific antagonist a-conotoxin-MII suppressed DA release evoked by single and low-frequency action potentials and concurrently enhanced release by high-frequency bursts in a manner similar to the b2*-selective antagonist dihydro-b-erythroidine (DHbE) in NAc, but less so in CPu. The greater role for a6*-nAChRs in NAc was not due to any confounding regional difference in ACh tone since elevated ACh levels (after the acetylcholinesterase inhibitor ambenonium) had similar outcomes in NAc and CPu. Rather, there appear to be underlying differences in nAChR subtype function in NAc and CPu. In summary, we reveal that a6b2*-nAChRs dominate the effects of nicotine on DA release in NAc, whereas in CPu their role is minor alongside other b2*-nAChRs (eg a4*), These data offer new insights to suggest striatal a6*-nAChRs as a molecular target for a therapeutic strategy for nicotine addiction.

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“…However, other nAChR subtypes are found in various amounts throughout many regions of the central nervous system (Marks et al, 1998;Perry et al, 2002), and some of these less prevalent receptors may play critical roles because of their strategic location (e.g., ␣6-containing receptors on dopamine axons) (Quik et al, 2002;Champtiaux et al, 2003;Salminen et al, 2004). Moreover, under some conditions in vivo, such as when ␣4␤2 and/or ␣7 receptors are desensitized or inactivated by exposure to nicotine or during certain disease states that may involve the loss of specific nAChR subtypes, the less prevalent receptors may take on critical roles in mediating cholinergic signals.…”

mentioning

confidence: 99%

The Nicotinic Receptor in the Rat Pineal Gland Is an α3β4 Subtype

Hernandez

Vicini²,

Xiao³

et al. 2004

Mol Pharmacol

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The rat pineal gland contains a high density of neuronal nicotinic acetylcholine receptors (nAChRs). We characterized the pharmacology of the binding sites and function of these receptors, measured the nAChR subunit mRNA, and used subunitspecific antibodies to establish the receptor subtype as defined by subunit composition. In ligand binding studies,binds with an affinity of ϳ100 pM to nAChRs in the pineal gland, and the density of these sites is ϳ5 times that in rat cerebral cortex. The affinities of nicotinic drugs for binding sites in the pineal gland are similar to those at ␣3␤4 nAChRs heterologously expressed in human embryonic kidney 293 cells. In functional studies, the potencies and efficacies of nicotinic drugs to activate or block whole-cell currents in dissociated pinealocytes match closely their potencies and efficacies to activate or block 86 Rb ϩ efflux in the cells expressing heterologous ␣3␤4 nAChRs. Measurements of mRNA indicated the presence of transcripts for ␣3, ␤2, and ␤4 nAChR subunits but not those for ␣2, ␣4, ␣5, ␣6, ␣7, or ␤3 subunits. Immunoprecipitation with subunit-specific antibodies showed that virtually all [3 H]EB-labeled nAChRs contained ␣3 and ␤4 subunits associated in one complex. The ␤2 subunit was not associated with this complex. Taken together, these results indicate that virtually all of the nAChRs in the rat pineal gland are the ␣3␤4 nAChR subtype and that the pineal gland can therefore serve as an excellent and convenient model in which to study the pharmacology and function of these receptors in a native tissue.Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels composed of ␣ and ␤ subunits. Nine ␣ (␣2-␣10) and three ␤ (␤2-␤4) subunits have been identified in vertebrates, and different subunit combinations define specific receptor subtypes. All of these subtypes pass Na ϩ , K ϩ , and Ca 2ϩ , but they exhibit distinct biophysical and pharmacological properties. Studies of nAChRs in Xenopus laevis oocytes and transfected mammalian cells have provided valuable information on the biophysical properties, pharmacology, and possible regulation of several different well-defined nAChR subtypes that might play important physiological roles. However, the precise subunit compositions of the subtypes of nAChRs that actually exist in most native tissues are not well-defined. Therefore, identifying the subunit composition of native nAChRs is a crucial step in establishing the physiological roles played by the different receptor subtypes that exist in vivo.Considerable progress has been made in determining the subunit composition of the predominant receptor subtypes in the rat forebrain, namely the ␣4␤2 subtype (Whiting and Lindstrom, 1987;Flores et al., 1992), which has high affinity for most agonists, and the ␣7 subtype, which has high affinity for ␣-bungarotoxin (␣-BTX) (Couturier et al., 1990;Schoepfer et al., 1990;Orr-Urtreger et al., 1997). However, other nAChR subtypes are found in various amounts throughout many regions of the central ...

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Differential nicotinic receptor expression in monkey basal ganglia: Effects of nigrostriatal damage

Cited by 25 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

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

The Nicotinic Receptor in the Rat Pineal Gland Is an α3β4 Subtype

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