-
Biomolecules Jun 2020It was a pleasure to receive a proposal to organize and be a guest editor of a Special Issue ofBiomolecules. This is the field in which I am working and personally know...
It was a pleasure to receive a proposal to organize and be a guest editor of a Special Issue ofBiomolecules. This is the field in which I am working and personally know some of the leadingscientists. My narrow field is the research on the peptide and protein neurotoxins from animalvenoms and their application as sophisticated tools for analysis of nicotinic acetylcholine receptors(nAChRs) [...].
Topics: Acetylcholine; Animals; Humans; Receptors, Cholinergic
PubMed: 32503306
DOI: 10.3390/biom10060852 -
Current Pharmaceutical Design 2016Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because... (Review)
Review
Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.
Topics: Acetylcholine; Animals; Cholinergic Agonists; Humans; Lung Neoplasms; Receptors, Muscarinic; Receptors, Nicotinic
PubMed: 26818857
DOI: 10.2174/1381612822666160127114237 -
British Journal of Pharmacology Jan 2006This article traces the development of knowledge about the physiology and pharmacology of acetylcholine and its receptors between 1930 and 2005, with emphasis on...
This article traces the development of knowledge about the physiology and pharmacology of acetylcholine and its receptors between 1930 and 2005, with emphasis on contributions by members of the British Pharmacological Society, and by other British pharmacologists and physiologists.
Topics: Acetylcholine; Animals; History, 20th Century; History, 21st Century; Humans; Neurotransmitter Agents; Receptors, Cholinergic; Societies, Scientific; United Kingdom
PubMed: 16402095
DOI: 10.1038/sj.bjp.0706474 -
Nature Reviews. Neuroscience Apr 2023Acetylcholine plays an essential role in fundamental aspects of cognition. Studies that have mapped the activity and functional connectivity of cholinergic neurons have... (Review)
Review
Acetylcholine plays an essential role in fundamental aspects of cognition. Studies that have mapped the activity and functional connectivity of cholinergic neurons have shown that the axons of basal forebrain cholinergic neurons innervate the pallium with far more topographical and functional organization than was historically appreciated. Together with the results of studies using new probes that allow release of acetylcholine to be detected with high spatial and temporal resolution, these findings have implicated cholinergic networks in 'binding' diverse behaviours that contribute to cognition. Here, we review recent findings on the developmental origins, connectivity and function of cholinergic neurons, and explore the participation of cholinergic signalling in the encoding of cognition-related behaviours.
Topics: Humans; Acetylcholine; Basal Forebrain; Cholinergic Agents; Cognition; Signal Transduction
PubMed: 36823458
DOI: 10.1038/s41583-023-00677-x -
The Journal of Pharmacology and... May 2019Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric...
Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric oxide (NO), have been identified. Acetylcholinesterase inhibitors, such as donepezil, can cause bleeding in patients, but the underlying mechanisms are not well understood. We hypothesized that acetylcholine is an endogenous inhibitor of platelets. We measured the effect of acetylcholine or analogs of acetylcholine on human platelet activation ex vivo. Acetylcholine and analogs of acetylcholine inhibited platelet activation, as measured by P-selectin translocation and glycoprotein IIb IIIa conformational changes. Conversely, we found that antagonists of the acetylcholine receptor, such as pancuronium, enhance platelet activation. Furthermore, drugs inhibiting acetylcholinesterase, such as donepezil, also inhibit platelet activation, suggesting that platelets release acetylcholine. We found that NO mediates acetylcholine inhibition of platelets. Our data suggest that acetylcholine is an endogenous inhibitor of platelet activation. The cholinergic system may be a novel target for antithrombotic therapies.
Topics: Acetylcholine; Blood Platelets; Humans; Nitric Oxide; Platelet Activation; Receptors, Cholinergic
PubMed: 30765424
DOI: 10.1124/jpet.118.253583 -
Topics in Current Chemistry (Cham) May 2023Acetylcholine (ACh) is one of the most crucial neurotransmitters of the cholinergic system found in vertebrates and invertebrates and is responsible for many processes... (Review)
Review
Acetylcholine (ACh) is one of the most crucial neurotransmitters of the cholinergic system found in vertebrates and invertebrates and is responsible for many processes in living organisms. Disturbances in ACh transmission are closely related to dementia in Alzheimer's and Parkinson's disease. ACh in biological samples is most often determined using chromatographic techniques, radioenzymatic assays, enzyme-linked immunosorbent assay (ELISA), or potentiometric methods. An alternative way to detect and determine acetylcholine is applying spectroscopic techniques, due to low limits of detection and quantification, which is not possible with the methods mentioned above. In this review article, we described a detailed overview of different spectroscopic methods used to determine ACh with a collection of validation parameters as a perspective tool for routine analysis, especially in basic research on animal models on central nervous system. In addition, there is a discussion of examples of other biological materials from clinical and preclinical studies to give the whole spectrum of spectroscopic methods application. Descriptions of the developed chemical sensors, as well as the use of flow technology, were also presented. It is worth emphasizing the inclusion in the article of multi-component analysis referring to other neurotransmitters, as well as the description of the tested biological samples and extraction procedures. The motivation to use spectroscopic techniques to conduct this type of analysis and future perspectives in this field are briefly discussed.
Topics: Animals; Acetylcholine; Spectrum Analysis
PubMed: 37169979
DOI: 10.1007/s41061-023-00426-9 -
American Journal of Physiology. Cell... Feb 2021The innate and adaptive immune systems play an important role in the development of cardiac diseases. Therefore, it has become critical to identify molecules that can... (Review)
Review
The innate and adaptive immune systems play an important role in the development of cardiac diseases. Therefore, it has become critical to identify molecules that can modulate inflammation in the injured heart. In this regard, activation of the cholinergic system in animal models of heart disease has been shown to exert protective actions that include immunomodulation of cardiac inflammation. In this mini-review, we briefly present our current understanding on the cardiac cellular sources of acetylcholine (ACh) (neuronal vs. nonneuronal), followed by a discussion on its contribution to the regulation of inflammatory cells. Although the mechanism behind ACh-mediated protection still remains to be fully elucidated, the beneficial immunomodulatory role of the cholinergic signaling emerges as a potential key regulator of cardiac inflammation.
Topics: Acetylcholine; Animals; Anti-Inflammatory Agents; Cardiotonic Agents; Heart; Heart Diseases; Humans; Inflammation; Neurons
PubMed: 33264077
DOI: 10.1152/ajpcell.00315.2020 -
Cellular and Molecular Life Sciences :... May 2007Sleep is regulated by homeostatic and circadian factors, and the regulation of sleep of mammals shares many molecular properties with the rest state of submammalian... (Review)
Review
Sleep is regulated by homeostatic and circadian factors, and the regulation of sleep of mammals shares many molecular properties with the rest state of submammalian species. Several brain structures take part in waking: the basal forebrain, posterior and lateral hypothalamus, and nuclei in the tegmentum and pons. Active sleep mechanisms are located to the preoptic/anterior hypothalamic area. In addition to acetylcholine and monoamines, glutamate and hypocretin/orexin are important waking factors. Gamma-aminobutyric acid and several peptide factors, including cytokines, growth hormone-releasing hormone and prolactin, are related to sleep promotion. Adenosine is an important homeostatic sleep factor acting in basal forebrain and preoptic areas through A1 and A2A receptors. Prolonged waking activates inducible nitric oxide synthase in the basal forebrain, which through energy depletion causes adenosine release and recovery sleep. Numerous genes have been found differentially displayed in waking compared with sleep, and they relate to neural transmission, synaptic plasticity, energy metabolism and stress protection. The genetic background of a few sleep disorders has been solved.
Topics: Acetylcholine; Animals; Brain; Brain Chemistry; Catecholamines; Gene Expression; Humans; Models, Anatomic; Sleep
PubMed: 17364141
DOI: 10.1007/s00018-007-6530-3 -
BMC Oral Health May 2022Sex hormones influence circulation, periodontitis, and wound healing. The aim of the study was to compare the endothelium-dependent and independent vasodilation in human...
BACKGROUND
Sex hormones influence circulation, periodontitis, and wound healing. The aim of the study was to compare the endothelium-dependent and independent vasodilation in human gingiva in men and women.
METHODS
Gingival blood flow was evaluated in twelve male and twelve female subjects with healthy gingiva and no systemic conditions after acetylcholine or nitric oxide donor (NitroPOHL). Agonists were administered into the gingival sulcus at the right secondary incisor (test site). Regional gingival blood flow (GBF) was imaged by Laser Speckle Contrast Imager from the marginal gingiva to the mucogingival junction in four consecutive regions (coronal, midway1, midway2 and apical). Blood flow was expressed in Laser Speckle Perfusion Unit (LSPU). The absolute maximal blood flow change (Dmax), the area under the blood flow curve (AUC), and the time to peak (TTP) were calculated.
RESULTS
Males had higher baseline GBF than females (257 ± 18.2 vs. 225 ± 18.8 LSPU, p < 0.001). Acetylcholine and NitroPOHL significantly increased the GBF in all test regions. The Dmax after the acetylcholine was reduced apically compared to the coronal (90 ± 13 LSPU vs. 117 ± 7 LSPU, p < 0.01), but it was similar after NitroPOHL (78 ± 9 LSPU vs. 86 ± 6 LSPU, p = 0.398) in both sexes. The Dmax and AUC were higher, and the TTP was smaller in men in most regions after acetylcholine but not after NitroPOHL.
CONCLUSION
In the human gingiva, the endothelium-independent vasodilation propagates without attenuation in the line of the vascular supply in both sexes. At the same time, the endothelium-dependent ascending vasodilation attenuates similarly in men and women. However, men had more pronounced endothelium-dependent vasodilation than women. Therefore, it might contribute to the increased severity of periodontal disease in men.
TRIAL REGISTRATION
The study was registered with ClinicalTrials.gov on 09.06.2021 (NCT04918563).
Topics: Acetylcholine; Endothelium; Female; Gingiva; Humans; Male; Regional Blood Flow; Vasodilation
PubMed: 35562729
DOI: 10.1186/s12903-022-02186-2 -
The Journal of General Physiology Feb 2023The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important...
The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.
Topics: Pituitary Adenylate Cyclase-Activating Polypeptide; Acetylcholine; Calcium; Catecholamines; Chromaffin Cells
PubMed: 36538657
DOI: 10.1085/jgp.202213180