Muscarinic acetylcholine receptor M1
Encyclopedia
The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor.
This receptor is found mediating slow EPSP
at the ganglion in the postganglionic nerve, is common in exocrine gland
s and in the CNS.
It is predominantly found bound to G proteins of class Gq
which 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.
, and, to a small extent, Gi
and Gs
. This results in slow EPSP and decreasedK+
conductance
This receptor is found mediating slow EPSP
Excitatory postsynaptic potential
In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
at the ganglion in the postganglionic nerve, is common in exocrine gland
Exocrine gland
Exocrine glands are a type of ductal glands that secrete their products into ducts that lead directly into the external environment...
s and in the CNS.
It is predominantly found bound to G proteins of class Gq
Gq alpha subunit
Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway...
which use upregulation of phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
C and therefore inositol trisphosphate and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX
Cholera toxin
Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...
or PTX
Pertussis toxin
Pertussis toxin is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection...
. However, Gi (causing a downstream decrease in cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
) 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
- EPSPExcitatory postsynaptic potentialIn neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
in autonomic ganglia - secretion from salivary glandSalivary glandThe salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
s - gastric acidGastric acidGastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...
secretion from stomachStomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is... - In CNSCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(memory?) - vagally-induced bronchoconstrictionBronchoconstrictionBronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus....
Mechanism
It couples to GqGq alpha subunit
Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway...
, and, to a small extent, Gi
Gi alpha subunit
Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...
and Gs
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...
. This results in slow EPSP and decreasedK+
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
conductance
Agonists
- acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
- carbacholCarbacholCarbachol , also known as carbamylcholine, is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
- CDD-0097
- McN-A-343 - mixed M1/M4 agonist
- L-689,660 - mixed M1/M3 agonist
- OxotremorineOxotremorineOxotremorine is a cholinomimetic that acts as a non-selective muscarinic acetylcholine receptor agonist.Oxotremorine produces ataxia, tremor and spasticity, similar to those symptoms seen in Parkinsonism, and has thus become a research tool in experimental studies aimed at determining more...
- VedaclidineVedaclidineVedaclidine is a novel analgesic drug which acts as a mixed agonist-antagonist at muscarinic acetylcholine receptors, being a potent and selective agonist for the M1 and M4 subtypes, yet an antagonist at the M2, M3 and M5 subtypes...
- XanomelineXanomelineXanomeline is a muscarinic acetylcholine receptor agonist with reasonable selectivity for the M1 and M4 subtypes, though it is also known to act as a M5 receptor antagonist...
- MuscarineMuscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
- 77-LH-28-177-LH-28-177-LH-28-1 is a recently discovered selective agonist of muscarinic acetylcholine receptor subtype 1 . It is an allosteric agonist, exhibiting over 100-fold specificity for M1 over other muscarinic receptor subtypes. 77-LH-28-1 penetrates the brain by crossing the blood brain barrier and is...
- brain penetrant selective M1 allosteric agonist
Antagonists
- atropineAtropineAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
- dicycloverine
- tolterodineTolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence.It is marketed by Pfizer in Canada and the United States by its brand name Detrol. In Egypt it is also found under the trade names Tolterodine by Sabaa and Incont L.A...
- oxybutyninOxybutyninOxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine...
- ipratropiumIpratropiumIpratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...
- mamba toxin muscarinic toxin 7Muscarinic toxin 7Muscarinic toxin 7 is part of a family of small peptides of 64 to 66 amino acid residuesderived from the venom of African mamba snakes , which target the different muscarinic receptor subtypes...
(MT7) - pirenzepinePirenzepinePirenzepine is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm. It is in a class of drugs known as muscarinic receptor antagonists - acetylcholine being the neurotransmitter of the parasympathetic nervous system which initiates the...
- telenzepineTelenzepineTelenzepine is an anticholinergic or sympatholytic used in the treatment of peptic ulcers. Telenzepine is atropisomeric, in other words the molecule has a stereogenic C–N-axis in neutral aqueous solution it displays a half-life for racemization of the order of 1000 years. The enantiomers have been...