Search results for " acetylcholine"
showing 10 items of 239 documents
Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid pl…
1999
Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the p…
Effects of scopolamine on dopamine neurons in the substantia nigra : role of the pedunculopontine tegmental nucleus
2009
Previous neurochemical and behavioral studies suggest that muscarinic receptor antagonism has an excitatory effect on the nigrostriatal dopamine (DA) system. Using in vivo extracellular single unit recording, this study examined whether blockade of the muscarinic receptor by scopolamine alters the firing properties of DA neurons in the substantia nigra (SN). Scopolamine was administered either systemically or locally to DA neurons using microiontophoresis. Surprisingly, scopolamine did not cause any significant change in either the firing rate or pattern of the spontaneously active DA neurons. However, systemic injection of scopolamine significantly increased the number of active DA neurons…
Muscarinic Properties of Compounds Related to Arecaidine Propargyl Ester
2011
A series of new analogues of the arecaidine propargyl ester (CAS 35516-99-5, APE, 1a) with alcohols consisting of 4 or 5 carbon atoms were investigated at muscarinic receptor subtypes. The muscarinic activity of the quaternary and tertiary salts of the APE-related compounds were assayed on the isolated guinea-pig ileum (M 3 receptor subtype) and guinea-pig left atria (M 2 receptor subtype) as well as on rabbit isolated vas deferens (M 1 receptor subtype). The structural variations made in the APE molecule, replacing the triple bond in the ester side chain with structures such as double bond, an allene moiety, a single bond, a cyclopropyl group or two triple bonds should alter the selectivit…
Prejunctional M1 and postjunctional M3 muscarinic receptors in the circular muscle of the guinea-pig ileum.
1995
The effects of subtype-selective muscarinic receptor antagonists on electrically evoked release of acetylcholine and muscle contraction were compared in circular muscle preparations of the guinea-pig ileum. Incubation of the preparation with [3H]choline resulted in the formation of [3H]acetylcholine. Electrical stimulation caused the release of [3H]acetylcholine which was abolished by tetrodotoxin and omission of calcium from the medium. 5-Hydroxytryptamine (10 microM) and the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (300 microM) did not change acetylcholine release. The muscarinic antagonists pirenzepine (M1 selective), AF-DX 116 (M2 selective) and hexahydrosiladifenidol (M3 se…
Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus
2019
AbstractRecently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS ex…
In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD
2011
Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspas…
The nACHR4 594C/T polymorphism in Alzheimer disease
2006
Alzheimer disease (AD) is the most common form of dementia with complex etiology and multifactorial origin. Although several neurochemical deficits have been described in AD patients, explanation of the nature of the cognitive disturbance is focused on the "cholinergic hypothesis." The neuronal nicotinic acetylcholine receptor (neuronal nAChR) belongs to the superfamily of ionic channel activated by ligand. This paper presents a population-based population association study, testing the hypothesis that variants of the nAChR gene confer genetic susceptibility to AD. The authors analyzed two cohorts constituted by 60 controls and 80 AD patients in which significant increase of 594T polymorphi…
Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
2010
Contains fulltext : 89305.pdf (Publisher’s version ) (Closed access) Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 x 10(-8)), including previously identified SNPs at 15q25 repre…
Nicotinic and muscarinic modulation of 5-hydroxytryptamine (5-HT) release from porcine and canine small intestine
1992
Strips of porcine and canine small intestine were incubated in vitro and the release of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. The spontaneous outflow of 5-HT from the porcine and canine small intestine largely reflects calcium-dependent 5-HT secretion from enterochromaffin cells which are under a spontaneous neuronal, excitatory input as indicated by the inhibitory effect (30-40%) of tetrodotoxin. In both species, nicotine enhanced the release of 5-HT in a concentration-dependent manner by a maximum of about 50% at 100 microM. This effect was blocked by the nicotine receptor antagonist hexamethonium, but not by the subtype-selective nicotine recep…
Cholinergic Responses of Ophthalmic Arteries in M3and M5Muscarinic Acetylcholine Receptor Knockout Mice
2009
PURPOSE. To determine the functional role of M 3 and M 5 muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. METHODS. Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M 3 and M 5 receptors, ophthalmic arteries from mice deficient in either subtype (M3R -/- , M5R -/- , respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy. RESULTS. With the use of real-time PCR, all five muscarinic receptor …