Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

Oda, Akira; Tanaka, Hidekazu

doi:10.4103/1673-5374.147943

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…Although activation of nicotinic receptors shows variable responses depending on the subunit composition, their activation usually produces membrane depolarization [ 128 ]. Among their functions, these receptors play a role in enhancing neuromodulation and release of different neurotransmitters such as glutamate and GABA [ 129 ]. They are especially vulnerable to the deposit of ß-amyloid peptide in the pathogenesis of Alzheimer’s disease, manifesting a down-regulation of these receptors in Alzheimer’s patients [ 129 ].…”

Section: Acetylcholinementioning

confidence: 99%

“…Among their functions, these receptors play a role in enhancing neuromodulation and release of different neurotransmitters such as glutamate and GABA [ 129 ]. They are especially vulnerable to the deposit of ß-amyloid peptide in the pathogenesis of Alzheimer’s disease, manifesting a down-regulation of these receptors in Alzheimer’s patients [ 129 ]. On the other hand, there are 5 subtypes of muscarinic receptors: M1, M2, M3, M4, and M5 that can be classified into 2 groups, depending on their associated G protein: M1, M3, and M5 are ligated to the family of G q/11 proteins [ 130 ] and their activation increases neuronal excitability [ 131 ], whereas M2 and M4 are joined to G i/o -type G proteins [ 130 ] and their activation produces postsynaptic inhibition [ 131 ].…”

Section: Acetylcholinementioning

confidence: 99%

“…Alterations in the cholinergic system are associated with the pathogenesis of different mental pathologies such as schizophrenia, major depression, or bipolar disorder. In fact, ACh receptor antagonists and inhibitors of acetylcholinesterase are used for the treatment of depressive symptoms and visual hallucinations [ 129 ].…”

Section: Acetylcholinementioning

confidence: 99%

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Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Gros

Mesonero

et al. 2021

JCM

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.

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Section: Acetylcholinementioning

confidence: 99%

Section: Acetylcholinementioning

confidence: 99%

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Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Gros

Mesonero

et al. 2021

JCM

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“…The physiological processes regulated by the nAChRs and the 5-HT 3 Rs are dependent on the specific ligand bound 41 . As illustrated in Figure 2 , the binding of exogenous agonists to the orthosteric site substantially influences the transition rates between three distinct functional states of the receptor: the closed, open and desensitized states 42 .…”

Section: Definition and Physiological Functionsmentioning

confidence: 99%

Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery

Cheng

Jiang

et al. 2015

Acta Pharmacol Sin

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The nicotinic acetylcholine receptors (nAChRs) and the 5-HT3 receptors (5-HT3Rs) are cation-selective members of the pentameric ligand-gated ion channels (pLGICs), which are oligomeric protein assemblies that convert a chemical signal into an ion flux through postsynaptic membrane. They are critical components for synaptic transmission in the nervous system, and their dysfunction contributes to many neurological disorders. The diverse subunit compositions of pLGICs give rise to complex mechanisms of ligand recognition, channel gating, and ion-selective permeability, which have been demonstrated in numerous electrophysiological and molecular biological studies, and unraveled by progress in studying the structural biology of this protein family. In this review, we discuss recent insights into the structural and functional basis of two cation-selective pLGICs, the nAChR and the 5-HT3R, including their subunit compositions, ligand binding, and channel gating mechanisms. We also discuss their relevant pharmacology and drug discovery for treating various neurological disorders. Finally, we review a model of two alternative ion conducting pathways based on the latest 5-HT3A crystal structure.

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“…Another mechanism by which sparteine causes hyperexcitability is the activation of nicotinic acetylcholine receptors, particularly the a3b2 nicotinic receptors found in the central nervous system, which produce influxes of Na + and effluxes of K + in addition to increasing glutamate release [66,68,69]. Additionally, both of these mechanisms have been demonstrated to produce persistent morphologic changes, excitotoxicity, neural damage and neurodegeneration [45,48,70,71].…”

Section: Mechanism Of Action Of Sparteinementioning

confidence: 99%

Sparteine as an anticonvulsant drug: Evidence and possible mechanism of action

Villalpando-Vargas

Medina‐Ceja

2016

Seizure

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Sparteine is a quinolizidine alkaloid extracted from Lupinus that has numerous pharmacological properties both in humans and animal models. In the central nervous system, sparteine reduces locomotor activity, has light analgesic effects, also has no effects on short-term memory or spatial learning and does not induce changes in behavior or electroencephalographic (EEG) activity. However, the anticonvulsant profile of sparteine is not fully characterized in experimental animals and there are no data in humans. Therefore, the present review focuses on the experimental evidence supporting the anticonvulsant action of sparteine in models of acute seizures and status epilepticus (SE), as well as its possible mechanisms of action. The evidence that supports the anticonvulsant effect of (-)-Sparteine sulfate includes the inhibition of seizures induced by maximal electro-stimulation, a delay in the onset of convulsive behavior and the prolongation of survival time in mice treated with pentylenetetrazole (PTZ). Additionally, sparteine delays the onset of convulsive behavior and decreases the severity and mortality of rats treated with PTZ and pilocarpine. Sparteine decreases amplitude and frequency or blocks the epileptiform activity induced by PTZ, pilocarpine and kainic acid. Sparteine may decrease hyperexcitability through the activation of the M2 and M4 subtypes of mAChRs, which is a probable mechanism of action that together with its systemic effects may favor its anticonvulsant effects against seizures and SE.

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Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

Cited by 12 publications

References 37 publications

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery

Sparteine as an anticonvulsant drug: Evidence and possible mechanism of action

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