Muscarinic acetylcholine receptor M1

Muscarinic acetylcholine receptor M1
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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. It is localized to 11q13.
This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.
It is predominantly found bound to G proteins of class Gq 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, Gi (causing a downstream decrease in cAMP) and Gs (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
Secretion from salivary glands
Gastric acid secretion from stomach
Via the central nervous system (especially within the brain); mediating certain core aspects of perception, attention, cognitive functioning and likely; memory consolidation. 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.
Cognitive flexibility
Synaptic plasticity modulation
Anxiety-like behavior and spontaneous working memory
Salivation
Task switching
Vagally-induced bronchoconstriction
Mediating olfactory behaviors and detection of “social odors” which have implications (for rodents) in aggression, mating, and social behavior.
Occurrence in free living amoebae
A structural but not sequential homolog of the human M1 receptor has been reported in Acanthamoeba castellanii and Naegleria fowleri. Antagonists of human M1 receptors (e.g. atropine, diphenhydramine) have been shown to exert anti-proliferative effects on these pathogens.
Mechanism
It couples to Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance. It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.
Ligands
Agonists
acetylcholine
carbachol
cevimeline
muscarine
oxotremorine
pilocarpine
vedaclidine
xanomeline
77-LH-28-1 - brain penetrant selective M1 allosteric agonist
CDD-0097
McN-A-343 - mixed M1/M4 agonist
L-689, L-660 - mixed M1/M3 agonist
Allosteric modulators
benzylquinolone carboxylic acid
BQZ-12
VU-0090157
VU-0029767
VU0467319
[3H]PT-1284- M1-selective PAM Radioligand
Antagonists
atropine
diphenhydramine
scopolamine
tramadol
dicycloverine
fluoxetine
hyoscyamine
ipratropium
mamba toxin muscarinic toxin 7 (MT7)
Many antipsychotics like olanzapine, quetiapine, clozapine, chlorpromazine
pirenzepine
oxybutynin
Benzatropine
telenzepine
paroxetine
Tricyclic and tetracyclic antidepressants like clomipramine, imipramine, mirtazapine, amitriptyline
tolterodine
Biperiden
See also
Muscarinic acetylcholine receptor
References
Further reading
External links
Muscarinic acetylcholine receptors