Search results for "acetylcholine receptor"
showing 10 items of 263 documents
A second pathway of activation of the Torpedo acetylcholine receptor channel
1991
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine (D-eserine) with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles and of equilibrium binding. We find that (-) physostigmine induces cation flux (and also binds to the receptor) even in the presence of saturating concentrations of antagonists of acetylcholine, such as D-tubocurarine, alpha-bungarotoxin or antibody WF6. The direct action on the acetylcholine receptor is not affected by removal of the methylcarbamate function from the drug and thus is not due to carbamylation of the receptor…
A muscarinic mechanism inhibiting the release of noradrenaline from peripheral adrenergic nerve fibres by nicotinic agents.
1968
Recent progress in understanding cholinergic function at the cellular and molecular levels
1992
Cholinergic transmission can claim to be the first form of chemical neurotransmission to be investigated by pharmacological and electrophysiological methods and the first in which both the transmitter and its receptor have been isolated and characterized. One reason for this is that neuromuscular transmission is cholinergic and the neuromuscular junction (especially that of frogs) is a readily investigated synapse in which responses are recorded by a muscular twitch — something which can be appreciated by direct observation and which does not require sophisticated equipment. Another is that in the form of the electric organs of strongly electric fish Nature has provided a tissue embryologic…
Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists.
2003
A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H(1) receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M(1)-M(5)) and for human histamine H(1) receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [(3)H]N-methylscopolamine ([(3)H]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M(2) receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved sel…
Expression and possible functions of the cholinergic system in a murine embryonic stem cell line.
2007
The expression of a cholinergic system during embryonic development is a widespread phenomenon. However, no precise function could be assigned to it during early pre-neural stages and there are only few studies that document when it precisely starts to be expressed. Here, we examined the expression of cholinergic components in a murine embryonic stem cell line by RT-PCR, histochemistry, and enzyme activity measurements; the acetylcholine (ACh) content was measured by HPLC. We have demonstrated that embryonic stem cells express ACh, acetylcholine receptors, choline acetyltransferase (ChAT), acetyl- and butyryl-cholinesterase (AChE and BChE). Butyryl-cholinesterase (BChE) expression was highe…
Detection of Fibroblast Growth Factor Receptor 1 (FGFR1) Transactivation by Muscarinic Acetylcholine Receptors (mAChRs) in Primary Neuronal Hippocamp…
2018
In addition to their canonical intracellular signals involved in the regulation of neuronal plasticity, G-protein coupled receptors can also rapidly transactivate tyrosine kinase receptors and their downstream intracellular signaling in absence of specific ligands. Here we describe our protocol for dissociating and maintaining hippocampal primary neurons in high- and low-density culture, followed by a description of methods employed to evaluate neurite outgrowth and protein phosphorylation associated with fibroblast growth factor receptor 1 transactivation by muscarinic acetylcholine receptors. Our goal was to provide the reader with detailed protocols of the abovementioned techniques and t…
A Role for the β1-β2Loop in the Gating of 5-HT3Receptors
2005
Based on theTorpedoacetylcholine receptor structure, Unwin and colleagues (Miyazawa et al., 2003; Unwin, 2005) hypothesized that the transduction of agonist binding to channel gate opening involves a “pin-into-socket” interaction between αV46 at the tip of the extracellular β1-β2loop and the transmembrane M2 segment and M2-M3 loop. We mutated to cysteine the aligned positions in the 5-HT3Aand 5-HT3Bsubunit β1-β2loops K81 and Q70, respectively. The maximal 5-HT-activated currents in receptors containing 5-HT3A/K81C or 5-HT3B/Q70C were markedly reduced compared with wild type. Desensitization of wild-type currents involved fast and slow components. Mutant currents desensitized with only the f…
Thermodynamics and kinetics of ion permeation in wild-type and mutated open active conformation of the human α7 nicotinic receptor
2020
Molecular studies of human pentameric ligand-gated ion channels (LGICs) expressed in neurons and at neuromuscular junctions are of utmost importance in the development of therapeutic strategies for neurological disorders. We focus here on the nicotinic acetylcholine receptor nAChR-α7, a homopentameric channel widely expressed in the human brain, with a proven role in a wide spectrum of disorders including schizophrenia and Alzheimer's disease. By exploiting an all-atom structural model of the full (transmembrane and extracellular) protein in the open, agonist-bound conformation we recently developed, we evaluate the free energy and the mean first passage time of single-ion permeation using …