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The Interactions Between Acetylcholine and T-Cells and Their Role in the Immune System: A Scoping Review.

Acetylcholine (ACh) exhibits immunomodulatory functions beyond its conventional role as a neurotransmitter. T-cells possess the highest expression of cholinergic machinery, suggesting that the cholinergic system exists and may be important within the immune structure and function. The aim of this review was to examine the literature on ACh and its role and function in T-cells as a foundation for understanding the immunomodulatory effects on T-cells. A three-stage search strategy was conducted across three major databases. Non-English publications and articles published before 1990 were exclude…

Alternative Pathways of Acetylcholine Release in the Colon: Role of High-Affinity Choline Transporters.

BACKGROUND: Cholinergic neuromuscular transmission is central to gastrointestinal (GI) motility and is traditionally attributed to calcium-dependent, vesicular acetylcholine (ACh) release from enteric neurons. However, non-quantal, calcium-independent mechanisms-possibly involving transporter-mediated ACh efflux-may also contribute to cholinergic signaling. AIM: To investigate both classical and alternative mechanisms of ACh release in the colon, focusing on the potential role of non-vesicular, transporter-dependent pathways in modulating smooth muscle contractility. METHODS: Experiments wer…

Dopamine and Acetylcholine in the Striatum: Circuit Interactions and Behavioral Control in Substance Use Disorders.

Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by persistent drug seeking and impaired behavioral contro … opamine, the cholinergic system has emerged as an important modulator of striatal circuit function. Acetylcholine and its receptors interact extensively with dopaminergic pathways, shaping striatal signaling dynamics and influencing learning and action selection, with particularly strong relevance for nicotine dependence. In this review, we discuss how striatal …

Нацеливание на α7-никотиновый ацетилхолиновый рецептор при множественном склерозе: последствия для иммуномодуляции и нейрозащиты.

Множественный склероз (MS) — хроническое иммунное расстройство, характеризующееся демиелинацией, аксонной дегенерацией и прогрессивной неврологической инвалидностью. Текущие методы лечения с целью изменения заболеваний (ДМТ) неадекватно решают проблемы нейродегенерации и отказа от ремиелинирования, особенно в прогрессивных СМ. α7-никотиновый ацетилхолиновый рецептор (α7-nAChR), являющийся ключевым посредником в холинергическом антивоспалительном пути, стал многообещающей терапевтической целью, которая соединяет иммуномодуляцию и нейрозащиту. Этот обзор синтезирует текущие данные о биологии, ра

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by demyelination, axonal degeneration, and progressive neurological disability. Current disease-modifying therapies (DMTs) inadequately address neurodegeneration and remyelination failure, particularly in progressive MS. The α7-nicotinic acetylcholine receptor (α7-nAChR), a key media…

The potential roles of nicotinic acetylcholine receptors in the pathogenesis of multiple sclerosis: A comprehensive review.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Growing evidence suggests that nicotinic acetylcholine receptors (nAChRs), key components of the cholinergic system, play an important role in regulating immune responses and neuroinflammation. In the present review, we summarize and critically evaluate experimental and clinical evidence supporting the involvement of nAChRs in MS pathogenesis. Particular emphasis is placed on receptor subtype-specific effects, including the anti-inflam…

A Systematic Review on Drugs Acting as Nicotinic Acetylcholine Receptor Agonists in the Treatment of Dementia.

Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine recepto…

Molecular regulatory effect of the ergot alkaloid methylergometrine on the α3β4 nicotinic acetylcholine receptor.

Methylergometrine has widely been used pharmacologically to treat conditions such as pain, addiction, vasoconstriction, migraines, and Parkinson's disease. Despite its side effects, it is used as a therapeutic agent and research material for various diseases based on its natural potential; however, the regulatory effect of its interaction with the nicotinic acetylcholine receptor (nAChR) has not yet been investigated. The α3β4 nAChR is an ion channel essential for neurotransmission within the sympathetic, parasympathetic, and autonomic nervous systems. Inhibiting the α3β4 nAChR can suppress ne…

Analyzing Fusion Pore Dynamics and Counting the Number of Acetylcholine Molecules Released by Exocytosis.

Acetylcholine (ACh) is a critical neurotransmitter influencing various neurophysiological functions. Despite its significance, quantitative methods with adequate spatiotemporal resolution for recording a single exocytotic ACh efflux are lacking. In this study, we introduce an ultrafast amperometric ACh biosensor that enables 50 kHz electrochemical recording of spontaneous single exocytosis events at axon terminals of differentiated cholinergic human SH-SY5Y neuroblastoma cells with sub-millisecond temporal resolution. Characterization of the recorded amperometric traces revealed seven distinct…

The human alpha7 nicotinic acetylcholine receptor is a host target for the rabies virus glycoprotein.

The rabies virus enters the nervous system by interacting with several molecular targets on host cells to modify behavior and trigger receptor-mediated endocytosis of the virion by poorly understood mechanisms. The rabies virus glycoprotein (RVG) interacts with the muscle acetylcholine receptor and the neuronal α4β2 subtype of the nicotinic acetylcholine receptor (nAChR) family by the putative neurotoxin-like motif. Given that the neurotoxin-like motif is highly homologous to the α7 nAChR subtype selective snake toxin α-bungarotoxin (αBTX), other nAChR subtypes are likely involved. The purpose…

BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders.

INTRODUCTION: Anxiety disorders are common, disabling psychiatric conditions associated with excessive worry, irritability, and physiological symptoms of stress. Following insufficient response to psychological therapies, first-line pharmacological treatments for anxiety disorders suffer from inconsistent efficacy, addiction, and intolerable side-effect profiles (e.g. sedation), especially when used inappropriately or contrary to evidence-based guidelines. Developing anxiolytics acting via cholinergic modulation may provide novel options for the treatment of anxiety disorders, without the draw

A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression.

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5…

Differential voltage-dependent modulation of the ACh-gated K+ current by adenosine and acetylcholine.

Inhibitory regulation of the heart is determined by both cholinergic M2 receptors (M2R) and adenosine A1 receptors (A1R) that activate the s … reover, IKACh did not exhibit relaxation. Contrarily, activation of the M2R-Gi/o-IKACh pathway with acetylcholine induced the typical relaxation of the current, which correlated with the clear voltage-dependent effect observed in the concentration-response curves (~2.8-fold EC50 increase with depolarization) and in the IKACh deactivation kinetics (τ = 1762 ± 11 …

Sex-related Differences in Patients with Positive Coronary Spasm as Identified by Acetylcholine Testing.

Objective A pathological acetylcholine (ACh) test was observed at lower ACh doses in females compared with males in European populations. We retrospectively analyzed the sex-related differences in Japanese patients with provoked positive spasm by ACh spasm provocation testing. Methods We performed the ACh spasm provocation tests in 1,854 patients from Jan 1991 until Mar 2019. ACh was injected in incremental doses of 20/50/100/200 μg into the left coronary artery and 20/50/80 μg into the right coronary artery. Positive spasm was defined as >90% stenosis and usual chest pain or ischemic ECG chan…

Muscle acetylcholine receptor conversion into chloride conductance at positive potentials by a single mutation.

Charge selectivity forms the basis of cellular excitation or inhibition by Cys-loop ligand-gated ion channels (LGICs), and is essential for physiological receptor function. There are no reports of naturally occurring mutations in LGICs associated with the conversion of charge selectivity. Here, we report on a CHRNA1 mutation (α1Leu251Arg) in a patient with congenital myasthenic syndrome associated with transformation of the muscle acetylcholine receptor (AChR) into an inhibitory channel. Performing patch-clamp experiments, the AChR was found to be converted into chloride conductance at positiv…

Diverse Effects of Noradrenaline and Adrenaline on the Quantal Secretion of Acetylcholine at the Mouse Neuromuscular Junction.

Despite the long history of investigations of adrenergic compounds and their biological effects, specific mechanisms of their action in distinct compartments of the motor unit remain obscure. Recent results have suggested that not only skeletal muscles but also the neuromuscular junctions represent important targets for the action of catecholamines. In this paper, we describe the effects of adrenaline and noradrenaline on the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal release in the motor nerve end…

The expression, localization and function of α7 nicotinic acetylcholine receptor in rat corpus cavernosum.

OBJECTIVES: Alpha7 nicotinic acetylcholine receptor (α7-nAChR), an emerging pharmacological target for a variety of medical conditions, is expressed in the most mammalian tissues with different effects. So, this study was designed to investigate the expression, localization and effect of α7-nAChR in rat corpus cavernosum (CC). METHODS & KEY FINDINGS: Reverse transcription polymerase chain reaction (RT-PCR) revealed that α7-nAChR was expressed in rat CC and double immunofluorescence studies demonstrated the presence of α7-nAChR in corporal neurons. The rat CC segments were mounted in organ bat…

The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass.

The nicotinic receptor α7nAchR reportedly regulates vagal nerve targets in brain and cardiac tissue. Here we show that nAchR7-/- mice exhibit increased bone mass due to decreased osteoclast formation, accompanied by elevated osteoprotegerin/RANKL ratios in serum. Vagotomy in wild-type mice also significantly increased the serum osteoprotegerin/RANKL ratio, and elevated bone mass seen in nAchR7-/- mice was reversed in α7nAchR/osteoprotegerin-doubly-deficient mice. α7nAchR loss significantly increased TNFα expression in Mac1-positive macrophages, and TNFα increased the osteoprotegerin/RANKL rati

No evidence of a role of the β4 subunit of the nicotinic acetylcholine receptor in alcohol-related behaviors.

BACKGROUND: Nicotinic acetylcholine receptors have gained attention in the last several years as mediators of alcohol-related behaviors. The genes that code for the α5, α3, and β4 subunits (Chrna5, Chrna3, and Chrnb4, respectively) map adjacent to each other on human chromosome 15/mouse chromosome 9. Genetic variants in this region have been associated with alcohol phenotypes and mice that overexpress these three subunits have reduced ethanol intake. In the present experiments, we examined the role of the Chrnb4 gene in three ethanol behaviors: consumption, ataxia, and sedation. Wildtype, hete…