An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the α7 subtype

Papke, Roger L.; Bencherif, Merouane; Lippiello, Patrick M.

doi:10.1016/0304-3940(96)12889-5

Cited by 259 publications

(112 citation statements)

References 11 publications

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“…During the last few years, choline has received much attention because it is a selective and full agonist of a-bungarotoxin-sensitive, a7 subunit-containing nicotinic Ž acetylcholine receptors Papke et al, 1989;Alkondon et . al., 1997;Frazier et al, 1998;Alkondon et al, 1999 .…”

Section: Discussionmentioning

confidence: 99%

Potentiation and inhibition of neuronal α4β4 nicotinic acetylcholine receptors by choline

Zwart

Vijverberg

2000

European Journal of Pharmacology

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The effects of choline on a4b4 nicotinic acetylcholine receptors, expressed in Xenopus oocytes, were investigated using the two-microelectrode voltage clamp technique. Particular attention was paid to the interaction between the effects of acetylcholine and choline. Choline was a low-affinity agonist of a4b4 receptors with an efficacy of 10% as compared to acetylcholine. Responses evoked by 1 mM acetylcholine were potentiated by low concentrations of choline and inhibited by ) 10 mM choline, resulting in a bell-shaped concentration-effect relationship. Conversely, the effects of choline on responses evoked by 300 mM acetylcholine resulted in a monophasic inhibition curve with an IC of 0.87 mM. The data were fitted by a two-site receptor occupation model, which accounts for 50 similar effects of various cholinergic ligands on heteromeric nicotinic receptors. The results indicate that the potentiation was a competitive effect, whereas the inhibition was due to a mixture of competitive and non-competitive effects. It is concluded that choline acts as a potent, endogenous co-agonist at heteromeric a4b4 nicotinic receptors. q

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Section: Discussionmentioning

confidence: 99%

Potentiation and inhibition of neuronal α4β4 nicotinic acetylcholine receptors by choline

Zwart

Vijverberg

2000

European Journal of Pharmacology

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“…Various ligands have been identified as selective agonists and antagonists for the α7-nAChR. In the adult rat, choline activates α7 receptors with a potency that is 10-fold lower than observed for ACh without any detectable effect at α4, α 2, β2, or β4 ACh receptor subtypes (Papke et al, 1996). In the mammalian brain, α7-nAChRs constitute one of the predominant nAChR subtypes and nicotine application to the ventral tegmental area, paired with postsynaptic stimulation, contributes to a form of long-term potentiation, an effect attributed to presynaptic α7-nAChRs on glutamatergic afferents (Jones and Wonnacott, 2004;Mansvelder and McGehee, 2000;Rousseau et al, 2005;Song et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

Cheng

Meck

2007

Brain Research

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Choline supplementation of the maternal diet has a long-term facilitative effect on timing and temporal memory of the offspring. To further delineate the impact of early nutritional status on interval timing, we examined effects of prenatal-choline supplementation on the temporal sensitivity of adult (6 mo) male rats. Rats that were given sufficient choline in their chow (CON: 1.1 g/kg) or supplemental choline added to their drinking water (SUP: 3.5 g/kg) during embryonic days (ED) 12-17 were trained with a peak-interval procedure that was shifted among 75%, 50%, and 25% probabilities of reinforcement with transitions from 18s -> 36s ->72s temporal criteria. Prenatalcholine supplementation systematically sharpened interval-timing functions by reducing the associative/non-temporal response enhancing effects of reinforcement probability on the Start response threshold, thereby reducing non-scalar sources of variance in the left-hand portion of the Gaussian-shaped response functions. No effect was observed for the Stop response threshold as a function of any of these manipulations. In addition, independence of peak time and peak rate was demonstrated as a function of reinforcement probability for both prenatal-choline supplemented and control rats. Overall, these results suggest that prenatal-choline supplementation facilitates timing by reducing impulsive responding early in the interval, thereby improving the superimposition of peak functions for different temporal criteria.

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“…18 However, in regard to the activation of neuronal nAChRs, we have shown that the minimal structure required is nothing more than the cationic quaternary ammonium ion alone, as in tetramethylammonium ion (TMA). 20 Elaborations of this minimal structure may produce changes in potency and/or selectivity, as in the case of choline, which becomes selective for the α7 nAChR, but is 10-fold less potent than either TMA or ACh. A number of lines of research suggest that α7 receptors tolerate extensive elaboration on the basic activation pharmacophore, within certain structural requirements.…”

Section: Discussionmentioning

confidence: 99%

The characterization of a novel rigid nicotine analog with α7-selective nAChR agonist activity and modulation of agonist properties by boron inclusion

Papke

Zheng

Horenstein

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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The α7 nAChR subtype is of particular interest as a potential therapeutic target since it has been implicated as a mediator of both cognitive and neuroprotective activity. The rigid nicotine analog ACME and the N-cyanoborane conjugate ACME-B are selective partial agonists of rat α7 receptors expressed in Xenopus oocytes, with no significant activation of either α3β4 or α4β2 receptors. ACME-B is both more potent and efficacious than ACME. The efficacies of ACME-B and ACME are approximately 26% and 10% of the efficacy of ACh, respectively. Similar Nconjugation of S(−)nicotine with cyanoborane decreased efficacy for α3β4 and α4β2 receptors, as well as for α7 nAChR. Structural comparison of ACME with the benzylidene anabaseines, another class of previously identified α7-selective agonists, suggests that they share a similar structural motif that may be applicable to other α7-selective agonists.

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An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the α7 subtype

Cited by 259 publications

References 11 publications

Potentiation and inhibition of neuronal α4β4 nicotinic acetylcholine receptors by choline

Potentiation and inhibition of neuronal α4β4 nicotinic acetylcholine receptors by choline

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

The characterization of a novel rigid nicotine analog with α7-selective nAChR agonist activity and modulation of agonist properties by boron inclusion

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