| 1987 |
CHRM1 (M1 muscarinic acetylcholine receptor) was identified as a member of a family of muscarinic receptor genes; cloned cDNAs were expressed in mammalian cells and shown to encode functional receptors with distinct ligand-binding properties and tissue-specific expression, featuring seven transmembrane segments and a large intracellular region. |
cDNA cloning from rat cerebral cortex library, expression in mammalian cells, ligand binding assays |
Science |
High |
3037705 3443095
|
| 1989 |
CHRM1 (m1 subtype) selectively couples to phosphatidylinositol (PI) hydrolysis, and activation of this pathway by carbachol stimulates DNA synthesis in primary brain-derived astrocytes and transfected CHO cells, establishing that CHRM1-mediated PI hydrolysis drives cell proliferation. |
Transfection of recombinant mAChR subtypes in CHO cells and brain-derived cell lines; carbachol stimulation; PI hydrolysis assay; [3H]-thymidine incorporation |
Nature |
High |
2739737
|
| 1991 |
CHRM1 (m1), together with m3 and m5 but not m2 or m4, acts as an agonist-dependent oncogene in NIH 3T3 cells; transformation requires receptor coupling to phosphatidylinositol hydrolysis, whereas m2/m4 subtypes coupled to adenylyl cyclase inhibition do not cause transformation. |
Transfection of individual human mAChR genes in NIH 3T3 cells; focus formation assay with carbachol; PI hydrolysis assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1905013
|
| 1992 |
Stimulation of CHRM1 (m1) and m3 receptors with carbachol in transfected HEK293 cells increases release of amyloid precursor protein (APP) derivatives within minutes; this process is blocked by the protein kinase inhibitor staurosporine, indicating that protein kinase activity mediates receptor-controlled APP processing. |
Transfection of HEK293 cells with muscarinic receptor genes; carbachol stimulation; APP derivative quantification by immunoassay; staurosporine inhibition |
Science |
High |
1411529
|
| 1994 |
Activated CHRM1 (m1) in NIH 3T3 cells induces Raf-1 kinase activation and ERK2 activity in a largely PKC-independent manner; dominant-negative Raf-1 (K375W) abolishes m1-mediated transformation, placing Raf-1 downstream of CHRM1 signaling. |
Transfected NIH 3T3 cells expressing human m1 receptor; carbachol stimulation; Raf-1 kinase activity assay using MEK substrate; phosphoamino acid analysis; dominant-negative Raf-1 co-transfection; PKC inhibition (GF 109203X, phorbol ester down-regulation) |
The Journal of biological chemistry |
High |
8063729
|
| 1994 |
CHRM1 (m1) and m3 receptors selectively activate Gq/11, while m2 selectively activates Gi2; all three subtypes also activate Gi1 and Gi3, but m1/m3 do so only at higher agonist concentrations, demonstrating subtype-selective G protein coupling with differential efficacies. |
Photolabeling of G protein alpha subunits with [α-32P]GTP azidoanilide in transfected HEK293 cell membranes; subtype-specific immunoprecipitation; carbachol dose-response |
Molecular pharmacology |
High |
8190105
|
| 2007 |
β-arrestins coordinate termination of CHRM1 (M1 muscarinic receptor) signaling by physically interacting with diacylglycerol kinases (DGKs) and recruiting this complex to activated M1 receptors, thereby accelerating DAG degradation to phosphatidic acid; β-arrestins are essential for agonist-stimulated DAG-to-PA conversion at activated M1 receptors. |
Co-immunoprecipitation of β-arrestin with DGKs; RNAi knockdown of β-arrestins; mass spectrometry identification; DAG/phosphatidic acid measurements after agonist stimulation; recruitment of β-arrestin-DGK complex to activated 7TMRs by imaging |
Science |
High |
17272726
|
| 2007 |
Extracellular tau protein promotes intracellular calcium increase in neuronal cells through CHRM1 (M1) and M3 muscarinic receptors; this effect is blocked by M1/M3-selective antagonists and is recapitulated in non-neuronal cells transfected with M1 or M3 cDNA, indicating tau acts on neurons via these receptors. |
Antagonist pharmacology (pirenzepine, 4-DAMP) in primary hippocampal/cortical neurons and neuroblastoma; transfection of M1/M3 cDNA in non-neuronal cells; intracellular calcium imaging |
Molecular and cellular neurosciences |
Medium |
18272392
|
| 2008 |
M1 muscarinic receptor (CHRM1) allosteric agonists (AC-42 and 77-LH-28-1) selectively activate M1 over other mAChR subtypes via an allosteric binding site; 77-LH-28-1 also acts as an agonist at native rat hippocampal M1 receptors, increasing cell firing and inducing gamma frequency network oscillations in vitro and in vivo. |
Calcium mobilization and inositol phosphate accumulation assays at recombinant mAChR subtypes; in vitro and in vivo electrophysiology in rat hippocampus |
British journal of pharmacology |
Medium |
18454168
|
| 2009 |
CHRM1 signaling via Gαq/11 is functionally altered in 'muscarinic receptor-deficit schizophrenia': agonist potency for Gq/11 stimulation is decreased while maximal Gq/11-[35S]GTPγS coupling is increased, indicating compensatory upregulation of receptor-G protein coupling efficiency in this subgroup. |
[35S]GTPγS-Gαq/11 immunocapture assay in postmortem human cortex membranes (Brodmann area 9); dose-response to orthosteric (oxotremorine-M) and allosteric (AC-42) agonists |
Neuropsychopharmacology |
Medium |
19404243
|
| 2010 |
Individual M1 muscarinic receptor (CHRM1) molecules are randomly distributed in the plasma membrane and dynamically interconvert between monomers and dimers on a timescale of seconds; approximately 30% exist as dimers at any given time with no evidence for higher-order oligomers. |
Total internal reflection fluorescence microscopy (TIRFM) single-molecule imaging in live CHO cells; two-color TIRFM for dimer confirmation; single-particle tracking (~30 ms / ~20 nm resolution) |
Proceedings of the National Academy of Sciences of the United States of America |
High |
20133736
|
| 2013 |
In Huntington's disease striatal cells, H3K9me3-dependent heterochromatin accumulates at the CHRM1 promoter, reducing CHRM1 gene expression and impairing Ca2+-dependent neuronal signal transduction. |
H3K9me3-ChIP genome-wide sequencing combined with RNA sequencing in STHdh Q7/7 and Q111/111 stable cell lines; platform integration analysis; Ca2+ signaling functional assay |
Acta neuropathologica |
Medium |
23455440
|
| 2016 |
Crystal structures of the M1 muscarinic acetylcholine receptor bound to the inverse agonist tiotropium revealed structural differences in orthosteric and allosteric binding sites compared to M2, M3, and M4 receptors, providing a molecular basis for drug selectivity; comparison across subtypes identified residue differences contributing to subtype-selective binding. |
X-ray crystallography of M1 receptor in complex with tiotropium; structural comparison with M2, M3, M4 crystal structures |
Nature |
High |
26958838
|
| 2018 |
Chrm1 and Chrm3 double knockout in mice chronically diminishes REM sleep to almost undetectable levels, and knockout of these two Gq-type muscarinic acetylcholine receptors phenocopies synaptic inhibition of TrkA+ cholinergic neurons, establishing that CHRM1 and CHRM3 are essential for REM sleep generation. |
Triple-target CRISPR knockout of Chrm1/Chrm3 in mice; polysomnographic sleep recording (EEG/EMG); chemogenetic synaptic inhibition of TrkA+ cholinergic neurons |
Cell reports |
High |
30157420
|
| 2021 |
Magnolol upregulates CHRM1 expression in SH-SY5Y cells treated with Aβ, and CHRM1 activation mediates protection against Tau hyperphosphorylation and apoptosis through the cAMP/PKA/CREB pathway; pharmacological inactivation of cAMP signaling reverses magnolol's protective effects. |
CCK-8 viability assay; qRT-PCR and western blotting for CHRM1 and pathway components; ELISA and western blotting for cAMP/PKA/CREB; caspase-3 activity and flow cytometry for apoptosis; siRNA or inhibitor of cAMP pathway |
Journal of natural medicines |
Low |
34705126
|
| 2022 |
DOPA inhibits melanocyte and melanoma cell proliferation by inhibiting CHRM1 signaling; pharmacologic CHRM1 antagonism depletes c-Myc and FOXM1, and both pharmacologic inhibition of CHRM1 and FOXM1 inhibit melanoma tumor growth in preclinical mouse models. |
High-throughput pharmacologic screen; in vivo CRISPR genetic screen; pharmacological CHRM1 antagonism; western blotting for c-Myc and FOXM1; preclinical mouse melanoma tumor models |
Science advances |
Medium |
36054350
|
| 2024 |
CHRM1 inhibits the TRPM8 cation channel via Gq/11 and phospholipase C-mediated depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), defining a novel CHRM1-TRPM8 signaling axis with anti-fibrotic effects in liver disease; CHRM1 activation produces strong anti-fibrotic effects in a patient-derived 3D MASH model. |
BRET-based biosensors in live cells; orthogonal genetic assays (CRISPR); high-content imaging; chemogenomic screening in patient-derived 3D liver organoid model; multi-omics |
Advanced science |
Medium |
39605182
|
| 2003 |
M1 muscarinic receptors (CHRM1) expressed in human intestinal L cells (NCI-H716) control GLP-1 secretion; selective M1 agonist McN-A-343 stimulates GLP-1 secretion dose-dependently, and pirenzepine (M1 antagonist) but not 4-DAMP (M3 antagonist) blocks bethanechol-stimulated GLP-1 release, confirming a functional role for CHRM1 in GLP-1 secretion. |
GLP-1 secretion assay in NCI-H716 human L cell line; selective agonists/antagonists for mAChR subtypes; western blot, immunohistochemistry, RT-PCR for receptor subtype expression confirmation |
Endocrinology |
Medium |
12810581
|