Is modulation of nicotinic acetylcholine receptors by melatonin relevant for therapy with cholinergic drugs?

Markus, Regina Pekelmann; Silva, Cláudia L. M.; Franco, Daiane Gil; Barbosa, Eduardo J. Mortani; Ferreira, Zulma S.

doi:10.1016/j.pharmthera.2010.02.009

Cited by 56 publications

(33 citation statements)

References 139 publications

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“…Interestingly, there are data to support an association between melatonin and the activity of nicotinic acetylcholine receptors. Melatonin increases the expression of ␣-bungarotoxine-sensi- tive nicotinic receptors and also potentiates their effects (21). However, in neurons of plexus submucosus, melatonin reversibly decreases the amplitude of nicotinic excitatory postsynaptic potentials, suggesting a blockade of nicotinic receptors (8).…”

Section: Discussionmentioning

confidence: 99%

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

Sommansson

Saudi

Nylander

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Sommansson A, Saudi WSW, Nylander O, Sjöblom M. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo. Am J Physiol Gastrointest Liver Physiol 305: G95-G105, 2013. First published May 2, 2013; doi:10.1152/ajpgi.00074.2013.-Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ϳ30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of 51 Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25-100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol-and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HClinduced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol-and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

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Section: Discussionmentioning

confidence: 99%

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

Sommansson

Saudi

Nylander

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…As highlighted above, melatonin is a significant positive regulator of the a7nAChr [90], suggesting that some of melatonin's effects in gut regulation may be mediated by its induction of the a7nAChr. Recent work shows that melatonin's protection against induced gut permeability is mediated, at least partly, by the a7nAChr [8].…”

Section: Gut Melatoninmentioning

confidence: 96%

“…Given that local paracrine and autocrine, as well as circadian, melatonin dampens astrocyte and mast cell reactivity, melatonin would also decrease BBBp and therefore the infiltration of invading leukocytes. It should be noted that melatonin is also a significant inducer of the alpha 7 nicotinic acetylcholine receptor (a7nAChr) [90], which, when activated, is a significant regulator of mitochondrial functioning and inflammasome activation [91], as well as being an inhibitor of glia and mast cell reactivity [92,93]. Mast cells are also a significant determinant of increases in human gut permeability to stress/ cortisol [6].…”

Section: Local Melatonin Synthesismentioning

confidence: 99%

The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions

Anderson¹,

Maes

2015

Advances in Integrative Medicine

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“…It requires investigation as to whether gut bacteria synthesize melatonin, including as to the role of host dietary factors in this. Some of the protection afforded by melatonin in gutbarrier maintenance is mediated by the a7nAChR (39), the level and activity of which can be upregulated by melatonin (40). Consequently, TRYCATs pathway activation that increases the a7nAChR antagonist, kynurenic acid, may also act to negate the gut-barrier effects of melatonin.…”

Section: Melatonergic Pathwaysmentioning

confidence: 99%

Breastfeeding and the gut-brain axis: is there a role for melatonin?

Anderson¹,

Vaillancourt²,

Maes

et al. 2017

Biomolecular Concepts

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The benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system. The melatonergic pathways are intimately associated with highly researched processes in the gut, gut microbiome and gut-brain axis. As the melatonergic pathways are dependent on the levels of serotonin availability as a necessary precursor, decreased melatonin is linked to depression and depression-associated disorders. The association of breastfeeding and the gut-brain axis with a host of medical conditions may be mediated by their regulation of processes that modulate depression susceptibility. The biological underpinnings of depression include increased levels of pro-inflammatory cytokines, oxidative stress, kynurenine pathway activity and dysregulation of the hypothalamic-pituitary adrenal axis, all of which can decrease melatonergic pathway activity. The inclusion of the melatonergic pathways in the biological interactions of breast milk and gut development has significant theoretical and treatment implications, as well as being important to the prevention of a host of infant-, child-and adult-onset medical conditions.

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Is modulation of nicotinic acetylcholine receptors by melatonin relevant for therapy with cholinergic drugs?

Cited by 56 publications

References 139 publications

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions

Breastfeeding and the gut-brain axis: is there a role for melatonin?

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