Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?

Gotti, Cecilia; Carbonnelle, Eric; Moretti, Milena; Zwart, Ruud; Clementi, Francesco

doi:10.1016/s0166-4328(00)00212-6

Cited by 49 publications

(32 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clear identification of the receptor subtypes underlying the beneficial effects of nicotine is made more onerous by the current lack of truly selective compounds and the difficulties associated with producing nAChR subtype selective drugs (Gotti et al, 2000;Broad et al, 2002). It has therefore been suggested that a combined approach of pharmacological interventions and transgenic animals may help delineate the nAChR subtypes involved (Gotti et al, 2000;Chapman, 2002).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

Young

Finlayson

Spratt

et al. 2004

Neuropsychopharmacol

209

174

View full text Add to dashboard Cite

In humans, nicotine has been shown to improve attention in both normal and impaired individuals. Observations in rats reflect some, but not all aspects of the nicotine-induced improvements in humans. To date these findings have not been replicated in mice. To examine the effect of nicotine on sustained attention in mice, we have established a version of the 5-choice serial reaction-time (5-CSR) task with graded levels of difficulty, based upon spatial displacement and a variable intertrial interval. Using this paradigm, microgram doses of nicotine produced a consistent reduction in the level of omissions and an improvement in proportion correct in normal mice. This improvement in sustained attention was made irrespectively of whether mice had previously received nicotine. In an attempt to elucidate which nicotinic acetylcholine receptor (nAChR) subtype(s) mediate this effect, we examined the performance of a7 nAChR knockout (KO) mice in the 5-CSR task. a7 nAChR KO mice not only acquired the task more slowly than their wild-type littermates, but on attaining asymptotic performance, they exhibited a higher level of omissions. In conclusion, by increasing the level of task difficulty, the performance of mice was maintained at sufficiently low levels to allow a demonstrable improvement in performance upon nicotine administration. Furthermore, as a7 KO mice are clearly impaired in the acquisition and asymptotic performance of this task, the a7 nAChR may be involved in mediating these effects of nicotine.

show abstract

Section: Introductionmentioning

confidence: 99%

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

Young

Finlayson

Spratt

et al. 2004

Neuropsychopharmacol

209

174

View full text Add to dashboard Cite

show abstract

“…nAChRs are divided into muscle (␣1, ␤1, ␥/⑀, and ␦) and neuronal AChRs (␣2-10 and ␤2-4), and neuronal AChRs are further subdivided into those that form homomeric receptors when expressed in heterologous systems (␣7-10) and those that form heteromeric receptors (␣2-6 and ␤2-4 in different combinations) (Gotti et al, 2000). The ␣8 nAChR subunit has not been studied since it is only expressed in the chicken (Rubboli et al, 1994).…”

mentioning

confidence: 99%

The Expression and Functional Role of Nicotinic Acetylcholine Receptors in Rat Adipocytes

Liu

Mizuta²,

Matsukura³

2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

To clarify whether nicotine has a direct effect on the function of adipocytes, we evaluated nicotinic acetylcholine receptor (nAChR) expression in adipocytes by reverse transcriptasepolymerase chain reaction (RT-PCR) and immunocytochemistry and the direct effects of nicotine on the production of adipocytokines by enzyme-linked immunosorbent assay and Western blot analysis. Receptor binding assays were performed using [3 H]nicotine. RT-PCR studies revealed that ␣1-7, 9, 10, ␤1-4, ␦, and ⑀ subunit mRNAs are expressed in adipocytes. Immunocytochemical experiments also suggested the presence of ␣7 and ␤2 subunits. The receptor binding assay revealed a binding site for nicotine (K d ϭ 39.2 ϫ 10 Ϫ9

show abstract

“…Furthermore, there is a substantial interest in developing subtype-selective agonists and antagonists that may have potential as therapeutic agents (Gotti et al, 2000;Dwoskin and Crooks, 2001).…”

mentioning

confidence: 99%

Effects of Ginsenoside Rg₂ on Human Neuronal Nicotinic Acetylcholine Receptors

Sala

Mulet²,

Choi³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Ginseng saponins, major active components of ginseng root used by folk medicine in the treatment of various diseases, produce multiple pharmacological responses having many effects on the central and peripheral nervous system. Specifically, ginsenoside Rg 2 has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg 2 on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed in Xenopus oocytes. Rg 2 did not affect the acetylcholine (ACh)-induced currents in ␣ 7 human receptors, however Rg 2 affected the peak currents, and mainly the desensitization of heteromeric receptors ␣ 3 ␤ 4 , ␣ 3 ␤ 2 , ␣ 4 ␤ 4 , and ␣ 4 ␤ 2 . Both effects, a diminution of peak current and an increase of desensitization, are dose-dependent and are very similar for all the receptors. The mechanism of action has been studied in more detail in ␣ 3 ␤ 4 and ␣ 4 ␤ 2 receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg 2 effects at high ACh concentrations, indicative of a noncompetitive antagonism. A lack of voltage dependence on the reduction of the peak currents induced by ACh also suggests that Rg 2 does not act as an open channel blocker of human nAChR. The results indicate that Rg 2 acts specifically on heteromeric human nAChRs modulating their desensitization and suggest a possible mechanism by which this saponin contributes to the multiple therapeutic effects of ginseng.

show abstract

Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?

Cited by 49 publications

References 66 publications

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

The Expression and Functional Role of Nicotinic Acetylcholine Receptors in Rat Adipocytes

Effects of Ginsenoside Rg₂ on Human Neuronal Nicotinic Acetylcholine Receptors

Contact Info

Product

Resources

About

Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?

Cited by 49 publications

References 66 publications

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

Nicotine Improves Sustained Attention in Mice: Evidence for Involvement of the α7 Nicotinic Acetylcholine Receptor

The Expression and Functional Role of Nicotinic Acetylcholine Receptors in Rat Adipocytes

Effects of Ginsenoside Rg2 on Human Neuronal Nicotinic Acetylcholine Receptors

Contact Info

Product

Resources

About

Effects of Ginsenoside Rg₂ on Human Neuronal Nicotinic Acetylcholine Receptors