Muscarinic acetylcholine receptor M1

The muscarinic acetylcholine receptor M₁, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor that in humans is encoded by the CHRM1 gene.^[5] It is localized to 11q13.^[5]

CHRM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5CXV
Identifiers
Aliases	CHRM1, HM1, M1, M1R, cholinergic receptor muscarinic 1
External IDs	OMIM: 118510; MGI: 88396; HomoloGene: 20189; GeneCards: CHRM1; OMA:CHRM1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q12.3 Start 62,908,679 bp[1] End 62,921,807 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 A Start 8,641,153 bp[2] End 8,660,951 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in prefrontal cortex middle temporal gyrus Brodmann area 9 right frontal lobe superior frontal gyrus nucleus accumbens postcentral gyrus cingulate gyrus anterior cingulate cortex putamen Top expressed in dentate gyrus of hippocampal formation granule cell superior frontal gyrus primary visual cortex hippocampus proper olfactory tubercle nucleus accumbens primary motor cortex piriform cortex prefrontal cortex perirhinal cortex More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity phosphatidylinositol phospholipase C activity G protein-coupled acetylcholine receptor activity neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential G protein-coupled serotonin receptor activity neurotransmitter receptor activity Cellular component axon terminus integral component of membrane postsynaptic membrane membrane postsynaptic density plasma membrane integral component of plasma membrane cell junction dendrite asymmetric synapse synapse Schaffer collateral - CA1 synapse glutamatergic synapse cholinergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane integral component of postsynaptic density membrane Biological process positive regulation of intracellular protein transport G protein-coupled receptor signaling pathway cognition regulation of locomotion synaptic transmission, cholinergic saliva secretion nervous system development neuromuscular synaptic transmission protein kinase C-activating G protein-coupled receptor signaling pathway adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway positive regulation of ion transport positive regulation of cell population proliferation phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway cell population proliferation regulation of vascular associated smooth muscle contraction signal transduction G protein-coupled acetylcholine receptor signaling pathway regulation of postsynaptic membrane potential G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger chemical synaptic transmission G protein-coupled serotonin receptor signaling pathway regulation of glial cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1128 12669 Ensembl ENSG00000168539 ENSMUSG00000032773 UniProt P11229 P12657 RefSeq (mRNA) NM_000738 NM_001112697 NM_007698 RefSeq (protein) NP_000729 NP_001106167 NP_031724 Location (UCSC) Chr 11: 62.91 – 62.92 Mb Chr 19: 8.64 – 8.66 Mb PubMed search [3] [4]
Wikidata
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This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,^[6] is common in exocrine glands and in the CNS.^[7][8]

It is predominantly found bound to G proteins of class G_q^[9][10] that use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G_i (causing a downstream decrease in cAMP) and G_s (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.

Effects

• EPSP in autonomic ganglia^{[citation needed]}
• Secretion from salivary glands
• Gastric acid secretion from stomach^[5]
• Via the central nervous system (especially within the brain); mediating certain core aspects of perception, attention, cognitive functioning and likely; memory consolidation.^[11][12] This is a notable component in regards to the M₁ receptor since it helps explain how pharmacological compounds which antagonize the receptor site can consistently produce mental states like delirium (a major disruption in attention and decrease in baseline-level cognitive functioning), as well as the perceptual alterations and conspicuous hallucinations experienced with deliriant drugs like Datura. As of 2015, the M₁ receptor remains the only known muscarinic receptor to have this effect of hallucinogenic delirium when its functionality is inhibited or antagonized.^[13]
• Cognitive flexibility
• Synaptic plasticity modulation
• Anxiety-like behavior and spontaneous working memory
• Task switching
• Vagally-induced bronchoconstriction^[5]
• Mediating olfactory behaviors and detection of "social odors" which have implications (for rodents) in aggression, mating, and social behavior.^[14]

Occurrence in free living amoebae

A structural but not sequential homolog of the human M1 receptor has been reported in Acanthamoeba castellanii^[15] and Naegleria fowleri.^[16] Antagonists of human M1 receptors (e.g. atropine, diphenhydramine) have been shown to exert anti-proliferative effects on these pathogens.

Mechanism

It couples to G_q, and, to a small extent, G_i and G_s. This results in slow EPSP and decreased K⁺ conductance.^[12][17] It is preassembled to the G_q heterotrimer through a polybasic c-terminal domain.^[9]

Ligands

Agonists

• Acetylcholine
• Arecoline
• Carbachol^[12]
• Cevimeline
• Itameline
• Muscarine
• Oxotremorine
• Pilocarpine^[18]
• Vedaclidine
• Xanomeline
• 77-LH-28-1 - brain penetrant selective M₁ allosteric agonist
• CDD-0097
• McN-A-343 - mixed M1/M4 agonist^[12]
• L-689, L-660 - mixed M1/M3 agonist

Allosteric modulators

• BQCA^[19]
• BQZ-12^[20]
• VU-0090157^[21]
• VU-0029767^[21]
• VU0467319^[22]
• [³H]PT-1284- M1-selective PAM Radioligand^[23]

Antagonists

• atropine^[12]
• diphenhydramine
• scopolamine^[24]
• tramadol^[25]
• dicycloverine^[12]
• fluoxetine
• hyoscyamine^[26]
• ipratropium^[12]
• mamba toxin muscarinic toxin 7 (MT7)^[12]
• Many antipsychotics like olanzapine, quetiapine, clozapine, chlorpromazine
• pirenzepine
• oxybutynin^[12]
• Benzatropine
• telenzepine
• paroxetine
• PIPE-359
• Tricyclic and tetracyclic antidepressants like clomipramine, imipramine, mirtazapine, amitriptyline
• tolterodine^[12]
• Biperiden^[27]

See also

• Muscarinic acetylcholine receptor