Search results for " acetylcholine"
showing 10 items of 239 documents
Novel Analgesic Agents Obtained by Molecular Hybridization of Orthosteric and Allosteric Ligands
2019
AbstractDespite the high incidence of acute and chronic pain in the general population, the efficacy of currently available medications is unsatisfactory. Insufficient management of pain has a profound impact on the quality of life and can have serious physical, psychological, social, and economic consequences. This unmet need reflects a failure to develop novel classes of analgesic drugs with superior clinical properties and lower risk of abuse. Nevertheless, recent advances in our understanding of the neurobiology of pain are offering new opportunities for developing different therapeutic approaches. Among those, the activation of M2 muscarinic acetylcholine receptors, which play a key ro…
Existence of muscarinic acetylcholine receptor (mAChR) and fibroblast growth factor receptor (FGFR) heteroreceptor complexes and their enhancement of…
2017
Abstract Background Recently, it was demonstrated that G-protein-coupled receptors (GPCRs) can transactivate tyrosine kinase receptors in absence of their ligands. In this work, driven by the observation that mAChRs and fibroblast growth factor receptors (FGFRs) share signalling pathways and regulation of brain functions, it was decided to explore whether mAChRs activation may transactivate FGFRs and, if so, to characterize the related trophic effects in cultured hippocampal neurons. Methods Oxotremorine-M transactivation of FGFRs and related trophic effects were tested in primary hippocampal neurons. Western blotting and in situ proximity ligation assay (PLA) were used to detect FGFR phosp…
Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease
2021
The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmenta…
Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients
2016
Background: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect. Methods: Human sputum and blood neutrophils were isolated from healthy individuals ( n = 37), patients with stable COPD ( n = 52) and th…
Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large…
2016
PLoS one 11(4), e0152984 (2016). doi:10.1371/journal.pone.0152984
The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats
2017
Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothel…
Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms
2016
Background Pancreatic polypeptide (PP) is supposed to be one of the major endogenous agonists of the neuropeptide Y4 receptor. Pancreatic polypeptide can influence gastrointestinal motility, acting mainly through vagal mechanisms, but whether PP acts directly on the stomach has not been explored yet. The aims of this study were to investigate the effects of PP on mouse gastric emptying, on spontaneous tone of whole stomach in vitro and to examine the mechanism of action. Methods Gastric emptying was measured by red phenol method after i.p. PP administration (1–3 nmol per mouse). Responses induced by PP (1–300 mmol L−1) on gastric endoluminal pressure were analyzed in vitro in the presence o…
Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in …
1997
1 The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M-2-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M-2 receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference.2 It was found that tripitramine antagonized …
Endogenous noradrenaline release from guinea-pig isolated trachea is inhibited by activation of M2 receptors
1992
Overflow of endogenous noradrenaline (NA) from guinea-pig isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses). The muscarinic receptor agonist oxotremorine inhibited the evoked overflow of NA in a concentration-dependent manner (EC50 84 nM). Methoctramine, pirenzepine and p-fluoro-hexahydrosiladiphenidol (each 1 microM) shifted the concentration-response curves of oxotremorine to the right with apparent pA2 values of 7.60, 6.74 and 6.18, respectively. It is concluded that sympathetic nerve terminals in the guinea-pig trachea are endowed with inhibitory muscarinic M2 receptors.
The effects of several muscarinic antagonists on pre- and postsynaptic receptors in the isolated rabbit heart
1981
In order to reveal possible differences between pre- and postsynaptic muscarine receptors, seven antagonists were tested for their affinities on these receptor sites in the rabbit isolated perfused heart. Methacholine was used as an agonist to inhibit the noradrenaline overflow evoked by electrical stimulation (3 Hz, 3 min) of the sympathetic nerves (presynaptic parameter) and to decrease the systolic tension development of the right atrium (postsynaptic parameter). The affinity of an antagonist was expressed as pA2. A decreasing order of potency was obtained with ipratropium, scopolamine, atropine, trihexyphenidyl, amitriptyline, and gallamine, both for pre- and postsynaptic responses. The…