The muscarinic acetylcholine receptor M₂, also known as the cholinergic receptor, muscarinic 2, is a

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

that in humans is encoded by the ''CHRM2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Multiple alternatively spliced transcript variants have been described for this gene.

Function

Heart

The M₂ muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...

, by slowing the speed of depolarization. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). However, they have little effect on the contractile forces of the ventricular muscle, slightly decreasing force.

IQ

A Dutch family study "a highly significant association" between the ''CHRM2''

and intelligence as measured by the Wechsler Adult Intelligence Scale-Revised. A similar association was found independently in the ''Minnesota Twin and Family Study''. However, a larger 2009 study attempting to replicate this claim instead found no significant association between the ''CHRM2'' gene and intelligence.

Olfactory behavior

Mediating

olfactory The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, it ...

guided behaviors (e.g. odor discrimination,

aggression Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...

, mating).

Mechanism of action

M₂ muscarinic receptors act via a G_i type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects. They appear to serve as autoreceptors. In addition, they modulate G protein-coupled inwardly-rectifying potassium channels. In the heart, this contributes to a decreased heart rate. They do so by the G_βγ subunit of the G protein; G_βγ shifts the open probability of K⁺ channels in the membrane of the cardiac pacemaker cells, which causes an outward current of potassium, effectively hyperpolarizing the membrane, which slows down the heart rate.

Ligands

Few highly selective M₂ agonists are available at present, although there are several non-selective muscarinic agonists that stimulate M₂, and a number of selective M₂ antagonists are available.

Agonists

* (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide (selective for M₂ but only partial agonist) *

Berberine Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydra ...

* Iper-8-Naph (alias N-8-Iper, bitopic/dualsteric agonist) * Methacholine * PAI ( photoswitchable agonist)

Antagonists

* AFDX-384 *

Atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

* Chlorpromazine * Dicycloverine * Dimenhydrinate * Dimethindene *

Diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into a vein ...

* Gallamine *

Hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including henbane, mandrake, angel's trumpets, jimsonweed ...

Ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms ...

* Methoctramine * Otenzepad * Oxybutynin * Thorazine * Tolterodine *

Trimipramine Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomn ...

References

External links

* * * {{DEFAULTSORT:Muscarinic Acetylcholine Receptor M2 Muscarinic acetylcholine receptors