Wild-type and alpha5 null mutant mice were used to identify nicotinic cholinergic receptors (nAChRs) that mediate alpha-conotoxin MII (alpha-CtxMII)-resistant dopamine (DA) release from striatal synaptosomes. Concentration-effect curves for ACh-stimulated release (20 s) were monophasic when wild-type synaptosomes were assayed but biphasic with synaptosomes from the alpha5 null mutant. Deleting the alpha5 gene also resulted in decreased maximal ACh-stimulated alpha-CtxMII-resistant DA release. When a shorter perfusion time (5 s) was used, biphasic curves were detected in both wild-type and alpha5 null mutants, indicative of high- and low-sensitivity (HS and LS) activity. In addition, DHbetaE-sensitive (HS) and DHbetaE-resistant (LS) components were found in both genotypes. These results indicate that alpha-CtxMII-resistant DA release is mediated by alpha4alpha5beta2, (alpha4)(2)(beta2)(3) (HS), and (alpha4)(3)(beta2)(2) (LS) nAChRs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386732 | PMC |
| http://dx.doi.org/10.1007/s12031-009-9263-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.
Transl Psychiatry
November 2024
Univ. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France.
Genome wide association and animal studies have implicated genetic variations in CHRNΑ5, encoding the α5 subunit-containing nicotinic acetylcholine receptors (α5*nAChRs), as a risk factor for developing alcohol use disorders (AUDs). To understand how α5*nAChR mutations may influence alcohol (EtOH) drinking behavior, we used a two-bottle choice procedure with intermittent access to alcohol in male and female transgenic mice expressing either the highly frequent human single nucleotide polymorphism (α5SNP/rs16969968) or a deletion of the Chrna5 gene (α5KO). AUDs-related preconsommatory traits (anxiety, sensation-seeking and impulsivity) were assessed with a battery of relevant tasks (elevated-plus maze, novel place preference and step-down inhibitory avoidance).
View Article and Find Full Text PDFCHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal.
Neuropharmacology
September 2023
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:
Nicotine is the principal psychoactive component in tobacco that drives addiction through its action on neuronal nicotinic acetylcholine receptors (nAChR). The nicotinic receptor gene CHRNA5, which encodes the α5 subunit, is associated with nicotine use and dependence. In humans, the CHRNA5 missense variant rs16969968 (G > A) is associated with increased risk for nicotine dependence and other smoking-related phenotypes.
View Article and Find Full Text PDFReceptor-binding domain of SARS-CoV-2 is a functional αv-integrin agonist.
J Biol Chem
March 2023
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA; Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. Electronic address:
Among the novel mutations distinguishing SARS-CoV-2 from similar coronaviruses is a K403R substitution in the receptor-binding domain (RBD) of the viral spike (S) protein within its S1 region. This amino acid substitution occurs near the angiotensin-converting enzyme 2-binding interface and gives rise to a canonical RGD adhesion motif that is often found in native extracellular matrix proteins, including fibronectin. Here, the ability of recombinant S1-RBD to bind to cell surface integrins and trigger downstream signaling pathways was assessed and compared with RGD-containing, integrin-binding fragments of fibronectin.
View Article and Find Full Text PDFnicotinic acetylcholine receptor subunits and their native interactions with insecticidal peptide toxins.
Elife
May 2022
Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom.
nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that represent a target for insecticides. Peptide neurotoxins are known to block nAChRs by binding to their target subunits, however, a better understanding of this mechanism is needed for effective insecticide design. To facilitate the analysis of nAChRs we used a CRISPR/Cas9 strategy to generate null alleles for all ten subunit genes in a common genetic background.
View Article and Find Full Text PDFCalreticulin exploits TGF-β for extracellular matrix induction engineering a tissue regenerative process.
FASEB J
December 2020
Division of Translational Medicine, Department of Medicine, New York University School of Medicine-Langone Health, New York, NY, USA.
Topical application of extracellular calreticulin (eCRT), an ER chaperone protein, in animal models enhances wound healing and induces tissue regeneration evidenced by epidermal appendage neogenesis and lack of scarring. In addition to chemoattraction of cells critical to the wound healing process, eCRT induces abundant neo-dermal extracellular matrix (ECM) formation by 3 days post-wounding. The purpose of this study was to determine the mechanisms involved in eCRT induction of ECM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!