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The Neuromuscular Junction
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The drug hemicholinium-3 inhibits the reuptake of choline at the presynaptic terminal, which depresses ACh synthesis because most of the choline needed for ACh synthesis is provided through reuptake of the choline resulting from hydrolysis of ACh in the synaptic cleft, and only a relatively small amount of choline is transported from the cell body. α-latrotoxin is an extremely potent neurotoxin, that is a poison of the nervous system, contained in the venom of the black widow spider. It causes massive exocytosis of ACh from presynaptic terminals either by forming open pores in the presynaptic membrane that allow the influx of Ca2+ and Na+ or by binding to special receptors, thereby initiating processes that lead to exocytosis. The depletion of ACh eventually leads to muscle paralysis. Botulinum toxin, produced by a bacterium found in poisoned foods, is one of the most toxic substances known. Only 2 ng of a form of this toxin, when injected intravenously, can kill a human adult by preventing ACh vesicles from fusing with the presynaptic membrane and releasing ACh into the synaptic cleft. Extremely small doses of other forms of this toxin, commercially known as Botox, are injected into the skin to relax muscles causing wrinkles. Botox is also used in the treatment of disorders caused by overactive muscle movement or conditions arising from hyperactivity of some nerves.
Role of muscarinic receptors in cardiovascular regulation in SHR
Published in H. Saito, Y. Yamori, M. Minami, S.H. Parvez, New Advances in SHR Research –, 2020
The studies of Brezenoff and Guiliano (1982) and Guiliano and Brezenoff (1987) suggest, that central cholinergic hyperactivity appears to play a role in the pathogenesis of SHR hypertension. SHR from 12 to 60 weeks of age showed a hypotensive response to hemicholinium-3, a drug which is able to block the uptake of choline thereby inhibiting the synthesis of acetylcholine and reducing the endogenous content of acetylcholine when administered intracerebroventricularly. These results would be consistent with the hypothesis, that a stimulated cholinergic activity in SHR is derived primarily through altered presynaptic mechanisms.
Physiology, Biochemistry, and Pathology of Neuromuscular Transmission
Published in Marc H. De Baets, Hans J.G.H. Oosterhuis, Myasthenia Gravis, 2019
Hemicholinium-3 (HC-3) is a useful tool that blocks ACh synthesis in nerve muscle preparations in vitro. HC-3 blocks the high affinity carrier for choline and is effective at concentrations in the order of 1 μM with little side effects on other cholinergic parameters. In contrast, drugs such as naphtylvinylpyridine and bromo-acetylcholine are not useful in intact preparations as a synthesis blocker, despite the fact that they are quite potent inhibitors of ChAT in homogenized preparations.
Role of the mucins in pathogenesis of COPD: implications for therapy
Published in Expert Review of Respiratory Medicine, 2020
Federica Lo Bello, Antonio Ieni, Philip M. Hansbro, Paolo Ruggeri, Antonino Di Stefano, Francesco Nucera, Irene Coppolino, Francesco Monaco, Giovanni Tuccari, Ian M. Adcock, Gaetano Caramori
Differentiation of mucin-secreting human airway epithelial cells grown at ALI by IL-13 can be prevented and reversed by anti-muscarinic (tiotropium) treatment, suggesting a direct role for non-neuronal acetylcholine [102,103]. Studies of animal models confirm this contention and show reduced mucin-secreting cell differentiation after anticholinergic treatment in COPD models [103]. In patients with chronic bronchitis and/or stable COPD it is debateable whether ipratropium, oxitropium and tiotropium significantly improve mucociliary clearance [104,105]. Hemicholinium-3, a potent and selective choline uptake blocker, has been demonstrated to reduce MUC5AC production in H292 human pulmonary mucoepidermoid carcinoma cells stimulated with cigarette smoke [92].