Search results for "Nicotinic acetylcholine receptor"
showing 10 items of 50 documents
α7 Nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus
2000
The present report provides new findings regarding modulation of gamma-aminobutyric acid (GABA) transmission by alpha7 nicotinic receptor activity in CA1 interneurons of rat hippocampal slices. Recordings were obtained from tight-seal cell-attached patches of the CA1 interneurons, and agonists were delivered to the neurons via a modified U-tube. Application for 6 s of the alpha7 nicotinic receptor-selective agonist choline (or =1 mM) to all CA1 interneurons tested triggered action potentials that were detected as fast current transients. The activity triggered by choline terminated well before the end of the agonist pulse, was blocked by the alpha7 nicotinic receptor antagonist methyllycaco…
Nicotinic Receptors in Human Brain
1994
A vast knowledge is currently available on the molecular biology and the pharmacology of nicotinic acetylcholine receptors (nAChR) in the mammalian central nervous system (CNS) (Sargent, 1993). Only few attempts have been made to approach the expression of nAChRs at the level of functional systems, considering the different cell types involved and their connectivity. This aspect is of particular importance in order to evaluate nAChR expression under pathological conditions. Histochemical techniques have proven to be useful since immunohistochemistry and in situ hybridization can be performed on human autopsy tissue and allow for a cell type-specific localization of nAChR proteins and nAChR …
Synthesis and in vitro evaluation of galanthamine derivatives for examination of nicotinic acetylcholine receptor system
2001
ISunmrary: The syntheses and radioactive labeling of several galanthamine derivatives, 6-O-demethyl-6-O-fluoroethylgalanthamine, 10-N-demethyl-lO-Nfluoroethylgalanthamine and N-methylgalanthaminium are reported. First ill vitro evaluations were carried out to determine their properties as allosterically potentiating ligands of nicotinic receptors. N-methylgalanthaminium was found to be a promising candidate for further investigations. The most commonly applied therapeutic approach to balance nicotinic cholinergic deficits in Alzheimer’s disease (AD) patients is the administration of acetylcholinesterase inhibitors (AChE-I) although they have been proven to be of limited therapeutic value [ …
Monoclonal antibodies FK1 and WF6 define two neighboring ligand binding sites on Torpedo acetylcholine receptor alpha-polypeptide.
1994
Previous studies have identified the sequence region flanking the invariant vicinal cysteinyl residues at positions 192 and 193 of the nicotinic acetylcholine receptor alpha-subunit as containing major elements of the binding site for acetylcholine and its agonists and antagonists, including antibody WF6 (Conti-Tronconi, B. M., Diethelm, B. M., Wu, X., Tang, F., Bertazzon, T., Schroder, B., Reinhardt-Maelicke, A., and Maelicke, A. (1991) Biochemistry 30, 2575-2584). Recently we have shown that the sequence region flanking lysine alpha 125 contains elements of the binding site for physostigmine and related ligands, including antibody FK1 (Schrattenholz, A., Godovac-Zimmerman, J., Schafer, H.…
<title>Spectroscopic investigation of the nicotinic acetylcholine receptor for application in medical diagnosis</title>
1998
Native vesicles containing the nicotinic acetylcholine receptor (nAChR) prepared from the electric organ of the ray Torpedo marmorata were used to obtain fluorescence signal sin dependence of different concentrations of the local anesthetics procaine. Nonlinear concentration dependent spectral changes are found using ethidium bromide as a fluorescence marker. Structural changes are found for the proteins including the nAChR in the vesicles during immobilization onto surfaces such as IR transparent germanium (GE) crystal, Ge crystal coated with silver (Ag) cluster to use the SEIRA effect and/or crystals covered with a lipid subphase. A comparison between Ge and Ge coated with Ag (Ge/Ag) clus…
Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer's disease
2000
The basic symptoms of Alzheimer's dementia, i.e., a loss in cognitive function, are due to impaired nicotinic cholinergic neurotransmission. To compensate for this impairment by drug treatment, blockers of the acetylcholine-degrading enzyme acetylcholinesterase are applied, even though this approach obviously is prone to many side-effects, including those of muscarinic nature. We have recently described a novel class of nicotinic acetylcholine receptor ligands which, similar to the action of benzodiazepines on GABA(A) receptors, allosterically potentiate submaximal nicotinic responses. The sensitizing effect is a consequence of facilitated channel opening in the presence of allosterically p…
Incorporation of the acetylcholine receptor dimer from Torpedo californica in a peptide supported lipid membrane investigated by surface plasmon and …
1998
Abstract The dimer species (Mr 580 000) of the nicotinic acetylcholine receptor, isolated from the electric organ of Torpedo californica, was incorporated into a thiopeptide supported lipid bilayer. The incorporation was achieved by fusion of liposomes with reconstituted receptor onto a gold-supported thiopeptide lipid monolayer. Surface plasmon resonance spectroscopy (SPS) was used to monitor in real time the fusion process as well as the specific binding of the antagonist α-bungarotoxin. A recently developed extension of SPS offering enhanced sensitivity and specificity, surface plasmon fluorescence spectroscopy (SPFS), was then used to monitor subsequent binding of the monoclonal WF6 and…
Cellular distribution in the rat telencephalon of mRNAs encoding for the alpha 3 and alpha 4 subunits of the nicotinic acetylcholine receptor.
1995
Pharmacological and electrophysiological studies provide evidence for the involvement of different nicotinic acetylcholine receptor isoforms in rat neocortical and hippocampal signal transduction. Yet, rather little is known on the cellular localization of these isoforms. With the availability of isoform specific nucleic acid probes and sensitive non-isotopic detection systems, nicotinic receptors can be studied on the mRNA level in individual neurons. In this way, we have paradigmatically studied the distribution of the alpha 3 and alpha 4 isoform mRNAs of the nicotinic receptor in the rat telencephalon. In the cerebral cortex, alpha 3 transcripts were mainly located in pyramidal neurons o…
The copy number variant involving part of the α7 nicotinic receptor gene contains a polymorphic inversion.
2008
The alpha7 nicotinic acetylcholine receptor gene (CHRNA7) is located at 15q13-q14 in a region that is strongly linked to the P50 sensory gating deficit, an endophenotype of schizophrenia and bipolar disorder. Part of the gene is a copy number variant, due to a duplication of exons 5-10 and 3' sequence in CHRFAM7A, which is present in many but not all humans. Maps of this region show that the two genes are in opposite orientation in the individual mainly represented in the public access human DNA sequence database (Build 36), suggesting that an inversion had occurred since the duplication. We have used fluorescent in situ hybridization to investigate this putative inversion. Analysis of inte…
The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration
2005
The physiologic mechanisms that determine directionality of lateral migration are a subject of intense research. Galvanotropism in a direct current (DC) electric field represents a natural model of cell re-orientation toward the direction of future migration. Keratinocyte migration is regulated through both the nicotinic and muscarinic classes of acetylcholine (ACh) receptors. We sought to identify the signaling pathway mediating the cholinergic regulation of chemotaxis and galvanotropism. The pharmacologic and molecular modifiers of the Ras/Raf-1/MEK1/ERK signaling pathway altered both chemotaxis toward choline and galvanotropism toward the cathode in a similar way, indicating that the sam…