Last update 01 Nov 2024

CHRNA2

Last update 01 Nov 2024

Basic Info

Synonyms

acetylcholine receptor, nicotinic, alpha 2 (neuronal), cholinergic receptor nicotinic alpha 2 subunit, cholinergic receptor, nicotinic alpha 2

+ [4]

Introduction

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Drugs associated with CHRNA2

Atracurium Besylate

Target

CHRNA2

Mechanism

CHRNA2 inhibitors

Active Org.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Originator Org.

Hospira, Inc.

Active Indication

Anesthesia

Inactive Indication

Muscle Hypotonia

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date23 Nov 1983

Tubocurarine Chloride

Target

5-HT3A receptor x CHRNA2

Mechanism

5-HT3A receptor antagonists [+1]

Active Org.-

Originator Org.

Bristol Myers Squibb Co.

Active Indication-

Inactive Indication

Muscle Hypotonia

Drug Highest PhaseWithdrawn

First Approval Ctry. / Loc.

First Approval Date28 Nov 1947

Clinical Trials associated with CHRNA2

CTRI/2024/03/064891 / Not yet recruitingPhase 2/3IIT

Comparative evaluation of ease of insertion of laryngeal mask airway supreme with laryngeal mask airway classic using low dose atracurium during general anaesthesia - Nil

Start Date10 Apr 2024

Sponsor / Collaborator-

CTRI/2024/01/061812 / Not yet recruitingNot ApplicableIIT

A prospective randomized Non-inferiority study to compare the quality of muscle relaxation using two different doses of Atracurium in patients under general anaesthesia at SMS Medical College, Jaipur - NIL

Start Date29 Jan 2024

Sponsor / Collaborator-

PACTR202405675858601 / CompletedNot Applicable

Low -dose Atracurium for Laryngeal Mask Airway Insertion in ophthalmic Surgeries

Start Date15 May 2023

Sponsor / Collaborator-

100 Clinical Results associated with CHRNA2

100 Translational Medicine associated with CHRNA2

0 Patents (Medical) associated with CHRNA2

115

Literatures (Medical) associated with CHRNA2

01 Sep 2024·Neurobiology of Learning and Memory

Hypersensitivity of the nicotinic acetylcholine receptor subunit (CHRNA2 ) in female adolescent mice produces deficits in nicotine-induced facilitation of hippocampal-dependent learning and memory

Article

Author: Mojica, Celina ; Wells, Alicia C ; Lotfipour, Shahrdad

Adolescence is characterized by a critical period of maturation and growth, during which regions of the brain are vulnerable to long-lasting cognitive disturbances. Adolescent exposure to nicotine can lead to deleterious neurological and psychological outcomes. Moreover, the nicotinic acetylcholine receptor (nAChR) has been shown to play a functionally distinct role in the development of the adolescent brain. CHRNA2 encodes for the α2 subunit of nicotinic acetylcholine receptors associated with CA1 oriens lacunosum moleculare GABAergic interneurons and is associated with learning and memory. Previously, we found that adolescent male hypersensitive CHRNA2^L9'S/L9' mice had impairments in learning and memory during a pre-exposure-dependent contextual fear conditioning task that could be rescued by low-dose nicotine exposure. In this study, we assessed learning and memory in female adolescent hypersensitive CHRNA2^L9'S/L9' mice exposed to saline or a subthreshold dose of nicotine using a hippocampus-dependent task of pre-exposure-dependent contextual fear conditioning. We found that nicotine-treated wild-type female mice had significantly greater improvements in learning and memory than both saline-treated wild-type mice and nicotine-treated CHRNA2^L9'S/L9' female mice. Thus, hyperexcitability of CHRNA2 in female adolescent mice ablated the nicotine-mediated potentiation of learning and memory seen in wild-types. Our results indicate that nicotine exposure during adolescence mediates sexually dimorphic patterns of learning and memory, with wild-type female adolescents being more susceptible to the effects of sub-threshold nicotine exposure. To understand the mechanism underlying sexually dimorphic behavior between hyperexcitable CHRNA2 mice, it is critical that further research be conducted.

15 Aug 2024·Biology of Reproduction

Neonicotinoids differentially modulate nicotinic acetylcholine receptors in immature and antral follicles in the mouse ovary

Article

Author: Mourikes, Vasiliki E ; Deviney, Ashley ; Neff, Alison ; Flaws, Jodi A ; Laws, Mary J ; Santacruz-Márquez, Ramsés

AbstractNeonicotinoids are the most widely used insecticides in the world. They are synthetic nicotine derivatives that act as nicotinic acetylcholine receptor agonists. Although parent neonicotinoids have low affinity for the mammalian nicotinic acetylcholine receptor, they can be activated in the environment and the body to positively charged metabolites with high affinity for the mammalian nicotinic acetylcholine receptor. Imidacloprid, the most popular neonicotinoid, and its bioactive metabolite desnitro-imidacloprid differentially interfere with ovarian antral follicle physiology in vitro, but their effects on ovarian nicotinic acetylcholine receptor subunit expression are unknown. Furthermore, ovarian nicotinic acetylcholine receptor subtypes have yet to be characterized in the ovary. Thus, this work tested the hypothesis that ovarian follicles express nicotinic acetylcholine receptors and their expression is differentially modulated by imidacloprid and desnitro-imidacloprid in vitro. We used polymerase chain reaction, RNA in situ hybridization, and immunohistochemistry to identify and localize nicotinic acetylcholine receptor subunits (α2, 4, 5, 6, 7 and β1, 2, 4) expressed in neonatal ovaries (NO) and antral follicles. Chrnb1 was expressed equally in NO and antral follicles. Chrna2 and Chrnb2 expression was higher in antral follicles compared to NO and Chrna4, Chrna5, Chrna6, Chrna7, and Chrnb4 expression was higher in NO compared to antral follicles. The α subunits were detected throughout the ovary, especially in oocytes and granulosa cells. Imidacloprid and desnitro-imidacloprid dysregulated the expression of multiple nicotinic acetylcholine receptor subunits in NO, but only dysregulated one subunit in antral follicles. These data indicate that mammalian ovaries contain nicotinic acetylcholine receptors, and their susceptibility to imidacloprid and desnitro-imidacloprid exposure varies with the stage of follicle maturity.

01 Jun 2024·Reproductive Toxicology

Effects of DDT and DDE on placental cholinergic receptors

Article

Author: Çelik, H Tolga ; Özdağ, Hilal ; Kuzukıran, Özgür ; Uyar, Recep ; Çinar, Özge Özgenç ; Turgut, Yağmur ; Özyüncü, Özgür ; Ceylan, Ahmet ; Ünal, M Altay ; Filazi, Ayhan ; Boztepe, Ümmü Gülsüm ; Yurdakök-Di Kmen, Begüm

The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44 μg/kg; 15.07 μg/kg and 189,42 μg/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine.

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CHRNA2

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