mAChR2
The M2 muscarinic acetylcholine receptor (mAChR2) functions as a G protein-coupled receptor that regulates acetylcholine signaling in both neuronal and non-neuronal cells[1]. Mechanistically, M2 modulates presynaptic neurotransmitter release via coupling to protein kinase C (PKC) and PDK1, selectively influencing PKCβI and PKCε isoforms and downstream SNARE machinery[2]. In the neuromuscular junction, M2 participates in developmental synapse elimination by regulating activity-dependent acetylcholine release, coordinating with M1/M4 mAChRs and adenosine receptors[3][4]. Beyond the nervous system, M2 receptors control epithelial and immune cell functions, including endocytosis-mediated receptor trafficking and signaling regulation[1]. In cardiac myocytes, M2 activation triggers endothelial nitric oxide synthase (eNOS)-dependent nitration of p190A RhoGAP, enhancing RhoA activity and altering cytoskeletal dynamics[5]. In disease models, down-regulation of M2 adversely affects Alzheimer’s disease-relevant genes, including BACE1, and disrupts amyloid precursor protein processing[5][6]. Compared with related muscarinic isoforms, M2 uniquely suppresses BACE1 expression, whereas M1 activation increases it[6]. Pharmacologically, selective M2 inhibitors, such as methoctramine, can block agonist-induced signaling in smooth muscle and macrophages, providing tools for dissecting M2-specific pathways[7][8]. These characteristics render M2 a critical target for experimental modulation in studies of synaptic plasticity, neurodegeneration, cardiac physiology, and immune regulation[1][2][5].
References:
- [1]. Züchner T, et al. Beta-secretase BACE1 is differentially controlled through muscarinic acetylcholine receptor signaling. J Neurosci Res. 2004 Jul 15;77(2):250-7. [Content Brief]
- [2]. de la Torre E, et al. Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice. Breast Cancer Res. 2005;7(3):R345-52. [Content Brief]
- [3]. Tsymbalyuk OV, et al. 8-[(4-benzylpiperazin-1-yl)methyl]-3-(2-chlorophenyl)-7-hydroxy-chromen-4-one is an activator of contractile activity of intestinal smooth muscles with reversible M2 cholinomimetic properties. Stud Biol. 2023;17(4):15-36.
- [4]. Ockenga W, et al. Non-neuronal functions of the m2 muscarinic acetylcholine receptor. Genes (Basel). 2013 Apr 2;4(2):171-97. [Content Brief]
- [5]. Nadal L, et al. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction. Mol Brain. 2016 Jun 23;9(1):67. [Content Brief]
- [6]. Cilleros-Mañé V, et al. M1 and M2 mAChRs activate PDK1 and regulate PKC βI and ε and the exocytotic apparatus at the NMJ. FASEB J. 2021 Jul;35(7):e21724. [Content Brief]
- [7]. Zuchner T, et al. Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins. J Neurochem. 2005 Oct;95(1):20-32. [Content Brief]
- [8]. Levay MK, et al. The Muscarinic Acetylcholine M2 Receptor-Induced Nitration of p190A by eNOS Increases RhoA Activity in Cardiac Myocytes. Cells. 2023 Oct 11;12(20):2432. [Content Brief]
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mAChR2 Related Products (58)
Related Products (58)
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Hexocyclium methylsulfate
0 ImagesHexocyclium methylsulfate is a potent mAChR antagonist with pKi values of 8.9, 7.7, 8.4, 8.8 for M1, M2, M3, and M4 subtype, respectively. Hexocyclium methylsulfate has the potential for the research of duodenal ulcer and irritable bowel syndrome.
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Ipratropium-d3 bromide
0 ImagesCat. No.: HY-B0241SPurity: 98.0%Synonyms: Sch 1000-d3Ipratropium-d3 (bromide) is the deuterium labeled Ipratropium bromide. Ipratropium bromide (Sch 1000) is a muscarinic receptor antagonist, with binding IC50 values of 2.9 nM, 2 nM, and 1.7 nM for M1, M2, and M3 receptors, respectively. Ipratropium bromide can be used in the research for COPD (chronic obstructive pulmonary disease) and asthma.
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p-F-HHSiD hydrochloride
0 ImagesSynonyms: p-Fluorohexahydrosiladifenidol hydrochloridep-F-HHSiD (p-Fluorohexahydrosiladifenidol) hydrochloride is a potent and selective M3 mAChR antagonist. p-F-HHSiD hydrochloride has antagonistic effects on other subtypes of the M receptor and the alpha1-adrenoceptor. p-F-HHSiD hydrochloride can be used for the researches of cancer, metabolic, neurological and cardiovascular disease such as, colon cancer, Alzheimer’s disease and diabetes.
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Trospium-d8 chloride
0 ImagesCat. No.: HY-B0461STrospium-d8 (chloride) is the deuterium labeled Trospium chloride. Trospium chloride is an orally active, specific and competitive antagonist of muscarinic cholinergic receptors (mAChRs), with antimuscarinic activity. Trospium chloride binds to muscarinic receptors M1, M2 and M3 with high affinity, but not nicotinic, cholinergic receptors.
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4-Piperidyl N-(2-biphenyl)carbamate
0 Images4-Piperidyl N-(2-biphenyl)carbamate (compound MA) is a competitive muscarinic acetylcholine receptor (mAChR) antagonist. 4-Piperidyl N-(2-biphenyl)carbamate exhibits higher affinity for M2 and M3 mAChR than β2AR (M2 pKi = 7.33; M3 pKi = 7.51; β2AR pKi = 4.94).
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Solifenacin D5 hydrochloride
0 ImagesCat. No.: HY-135329CAS No.: 1426174-05-1Solifenacin D5 hydrochloride is a deuterium labeled Solifenacin hydrochloride. Solifenacin hydrochloride is a muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.
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Milameline hydrochloride
0 ImagesCat. No.: HY-107650CAS No.: 139886-04-7Synonyms: CI 979 hydrochloride; RU 35926 hydrochlorideMilameline (CI 979; RU35926) hydrochloride is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline hydrochloride has equal affinity for different subtypes of human muscarinic receptors with IC50 of 1.3 µM for M1-, 1.1 µM for M2-, 1.5 µM for M3-, and 1.9 µM for M4-muscarinic receptors. Milameline hydrochloride has a higher affinity for sites [3H]CMD (IC50 = 20 nM), than [3H]QNB, (IC50 = 3059 nM). Milameline hydrochloride produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine (HY-N0296). Milameline hydrochloride can be used for the study of Alzheimer’s Disease.
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Lu AE51090
0 ImagesLu AE51090 is selective muscarinic M1 receptor agonist with blood-brain barrier penetration. Lu AE51090 activates human M1 receptor with EC50 of 61 nM, while showing no significant agonism at M2-M5 receptors. Lu AE51090 exerts procognitive effects in mice. Lu AE51090 can be used for the study of Alzheimer’s disease (AD) and cognitive impairment associated with schizophrenia (CIAS).
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YM-58790 free base
0 ImagesCat. No.: HY-101679ACAS No.: 168830-70-4YM-58790 free base is a potent antagonist of mAChR. YM-58790 free base binds M1, M2, M3 with Ki values of 28 nM, 260 nM, and 15 nM. YM-58790 free base exhibits potent inhibitory activity on bladder pressuer in reflexly-evoked rhythmic contraction in rats.
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PTAC oxalate
0 ImagesCat. No.: HY-107656CAS No.: 201939-40-4PTAC oxalate is a selective muscarinic receptor ligand. PTAC oxalate is an partial agonist of M2 and M4 but antagonist of M1, M3, and M5 (Ki values of 0.2-2.8 nM for hM1-5 in CHO cells). PTAC oxalate alleviates the mechanical allodynia on the neuropathic pain and has antidepression effects.
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LAS190792
0 ImagesCat. No.: HY-148527CAS No.: 1347232-69-2Synonyms: AZD8999LAS190792 is a bifunctional muscarinic acetylcholine receptor (mAChR) antagonist and β2-adrenergic receptor agonist. LAS190792 has a pIC50 of 8.8 against human M3 muscarinic receptor and a pIC50 of 9.1 against human β2-adrenergic receptor. LAS190792 exhibits vasodilatory and anti-inflammatory activities, and induces sustained bronchodilation in dogs. LAS190792 inhibits the release of IL-8, MMP9, IL-1β and GM-CSF from lipopolysaccharide-stimulated neutrophils. LAS190792 can be used in research related to respiratory system diseases.
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DIBA-Cy5
0 ImagesCat. No.: HY-151801DIBA-Cy5 is a fluorescent DIBA antagonist made up be DIBA-alkyne binding Cyanine5 fluorophores (Cy5) and polyethylene glycol (PEG) biomolecules. DIBA-Cy5 can serve as a fluorescent ligand, suitable for probe attachment through click chemistry. DIBA-Cy5 exerts a high binding affinity to type-2 mAChR (M2R) with the Kd value of 1.80 nM, can directly stain M2R receptors in the sinoatrial node of a mouse heart.
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Milameline
0 ImagesCat. No.: HY-135460CAS No.: 139886-32-1Synonyms: CI-979; RU35926Milameline (CI-979; RU35926) is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline has equal affinity for different subtypes of human muscarinic receptors with IC50 of 1.3 µM for M1-, 1.1 µM for M2-, 1.5 µM for M3-, and 1.9 µM for M4-muscarinic receptors. Milameline has a higher affinity for sites [3H]CMD (IC50 = 20 nM), than [3H]QNB, (IC50 = 3059 nM). Milameline produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine (HY-N0296). Milameline can be used for the study of Alzheimer’s Disease.
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Lu 26-046
0 ImagesCat. No.: HY-120329CAS No.: 143756-51-8Lu 26-046 is the agonist for muscarinic M1 receptor and M2 receptor and a weak antagonist for M3 receptor, with Ki of 0.51, 26 and 5 nM, respectively. Lu 26-046 exhibits specific stimulus property, that can be recognized by rats.
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J 104129 fumarate
0 ImagesCat. No.: HY-107653CAS No.: 257603-40-0J 104129 fumarate is a selective and orally active muscarinic M3 antagonist with Ki values of 4.2 nM and 490 nM for M3 and M2, respectively. J 104129 fumarate antagonized ACh-induced bronchoconstriction. J 104129 fumarate has the potential for the research of obstructive airway disease.
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Gallamine
0 ImagesGallamine is an allosteric, selective muscarinic M2 acetylcholine receptor antagonist (EC50: 130 nM for [3H]NMS dissociation from porcine muscarinic M2 receptors). Gallamine is also an acetylcholinesterase inhibitor (IC50s : 1070 μM, 1480 μM, 235 μM for EeAChE, hAChE, hBChE, respectively (in the absence of MeCN)). Gallamine increases free norepinephrine levels. Gallamine can be used as a muscle relaxant.
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Milameline hydroiodide
0 ImagesCat. No.: HY-107650ASynonyms: CI 979 hydroiodide; RU 35926 hydroiodideMilameline (CI 979; RU35926) hydroiodide is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline hydroiodide has equal affinity for different subtypes of human muscarinic receptors with IC50 of 1.3 µM for M1-, 1.1 µM for M2-, 1.5 µM for M3-, and 1.9 µM for M4-muscarinic receptors. Milameline hydroiodide has a higher affinity for sites [3H]CMD (IC50 = 20 nM), than [3H]QNB, (IC50 = 3059 nM). Milameline hydroiodide produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine (HY-N0296). Milameline hydroiodide can be used for the study of Alzheimer’s Disease.
