Rhesus monkey α7 nicotinic acetylcholine receptors: Comparisons to human α7 receptors expressed in Xenopus oocytes

Papke, Roger L.; McCormack, Thomas J.; Jack, Brian A.; Wang, Daguang; Bugaj-Gaweda, Bozena; Schiff, Hillary C.; Buhr, Joshua D.; Waber, Amanda; Stokes, Clare

doi:10.1016/j.ejphar.2005.08.043

Cited by 13 publications

(15 citation statements)

References 25 publications

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“…Interestingly, our data show that choline concentrations that suppress TNF release from these endotoxin-stimulated immune cells are significantly higher than acetylcholine concentrations (in the presence of an acetylcholinesterase inhibitor) that exert similar suppressive effects (3,4). These observations are in line with studies showing a lower agonistic efficacy of choline on neuronal α7nAChRs as compared with acetylcholine (14,27,28) and have implications for signaling after acetylcholine release, because choline can persist after acetylcholine degradation.…”

Section: Discussionsupporting

confidence: 79%

Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling

Parrish

Rosas-Ballina

Gallowitsch-Puerta

et al. 2008

Mol Med

293

205

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The α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) is an essential component in the vagus nerve-based cholinergic anti-inflammatory pathway that regulates the levels of TNF, high mobility group box 1 (HMGB1), and other cytokines during inflammation. Choline is an essential nutrient, a cell membrane constituent, a precursor in the biosynthesis of acetylcholine, and a selective natural α7nAChR agonist. Here, we studied the anti-inflammatory potential of choline in murine endotoxemia and sepsis, and the role of the α7nAChR in mediating the suppressive effect of choline on TNF release. Choline (0.1-50 mM) dosedependently suppressed TNF release from endotoxin-activated RAW macrophage-like cells, and this effect was associated with significant inhibition of NF-κB activation. Choline (50 mg/kg, intraperitoneally [i.p.]) treatment prior to endotoxin administration in mice significantly reduced systemic TNF levels. In contrast to its TNF suppressive effect in wild type mice, choline (50 mg/kg, i.p.) failed to inhibit systemic TNF levels in α7nAChR knockout mice during endotoxemia. Choline also failed to suppress TNF release from endotoxin-activated peritoneal macrophages isolated from α7nAChR knockout mice. Choline treatment prior to endotoxin resulted in a significantly improved survival rate as compared with saline-treated endotoxemic controls. Choline also suppressed HMGB1 release in vitro and in vivo, and choline treatment initiated 24 h after cecal ligation and puncture (CLP)-induced polymicrobial sepsis significantly improved survival in mice. In addition, choline suppressed TNF release from endotoxin-activated human whole blood and macrophages. Collectively, these data characterize the anti-inflammatory efficacy of choline and demonstrate that the modulation of TNF release by choline requires α7nAChR-mediated signaling.

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Section: Discussionsupporting

confidence: 79%

Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling

Parrish

Rosas-Ballina

Gallowitsch-Puerta

et al. 2008

Mol Med

293

205

View full text Add to dashboard Cite

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“…The α7-nicotinic receptor is activated by acetylcholine in adults, but in fetuses, cholinergic innervation does not reach thecerebrum untilnear birth, despite thereceptor’s appearance at the earliest stage of neuronal development (13, 14). Choline at millimolar levels is an effective agonist (15, 16). Millimolar levels of choline are normally present in the amniotic fluid, but high fetal demands for choline for the membrane phospholipids required for fetal growth can overwhelm the mother’s ability to supply fetal needs through synthesis and dietary intake (17).…”

mentioning

confidence: 99%

Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation

Ross

Hunter

Hoffman

et al. 2016

AJP

109

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Objective α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness. Method The authors previously reported that newborns in the phosphatidylcholine treatment group have increased suppression of the cerebral evoked response to repeated auditory stimuli. In this follow-up, they report parental assessments of the children’s behavior at 40 months of age, using the Child Behavior Checklist. Results At 40 months, parent ratings of children in the phosphatidylcholine group (N=23) indicated fewer attention problems and less social withdrawal compared with the placebo group (N=26). The improvement is comparable in magnitude to similar deficits at this age associated with later schizophrenia. The children’s behavior is moderated by CHRNA7 variants associated with later mental illness and is related to their enhanced cerebral inhibition as newborns. Conclusions CHRNA7, the α7-nicotinic acetylcholine receptor gene, has been associated with schizophrenia, autism, and attention deficit hyperactivity disorder. Maternal phosphatidylcholine treatment may, by increasing activation of the α7-nicotinic acetylcholine receptor, alter the development of behavior problems in early childhood that can presage later mental illness.

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“…However, to do so would require as full a characterization of concentration-dependent aspects of the receptor mediated response as we provide here for rat and human a7 nAChR. We have tested a number of agonists on a7 receptors cloned from Rhesus monkey and all the agonists tested, including ACh, were less potent for monkey a7 than for the human and rat a7 receptors (Papke et al, 2005b). Because the ACh controls were at a different functional concentration, single-concentration analysis of monkey a7 receptors would use different curves and formulae (not shown), but would nonetheless be easily done.…”

Section: Discussionmentioning

confidence: 98%

“…The average ACh EC 50 value reported in papers (Papke et al, 2005b;Papke and Papke, 2002;Placzek et al, 2004;Stokes et al, 2004) from our laboratory (n = 5) on either rat or human a7 receptors has been 26.3 AM. In spite of the fact that these papers spanned several years and utilized many different frogs as source for oocytes, the standard deviation in our EC 50 estimates has been only 7.6 AM.…”

Section: Comparisons Of Two Response Measuresmentioning

confidence: 98%

Rhesus monkey α7 nicotinic acetylcholine receptors: Comparisons to human α7 receptors expressed in Xenopus oocytes

Cited by 13 publications

References 25 publications

Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling

Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling

Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation

Estimation of both the potency and efficacy of α7 nAChR agonists from single-concentration responses

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