Muscarinic acetylcholine receptor M3

The muscarinic acetylcholine receptor M3, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is encoded by the human gene CHRM3.

The M3 muscarinic receptors are located at many places in the body, e.g. smooth muscles, endocrine, in exocrine glands, as well as in the lungs. They are also found in the CNS, where it induces emesis They generally cause smooth muscle contraction and increased glandular secretions.

They are unresponsive to PTX and CTX.

Mechanism
Like the M1 muscarinic receptor, M3 receptors are G proteins of class Gq which upregulate phospholipase C and therefore inositol trisphosphate and intracellular calcium as a signalling pathway. The calcium function in humans also involves activation of protein kinase C and its effects.

Smooth muscle
Because the M3 receptor is Gq-coupled and mediates an increase in intracellular calcium, it typically causes constriction of smooth muscle, such as that observed during bronchoconstriction. However, with respect to vasculature, activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle M3 mediates vasoconstriction in pathologies whereby the vascular endothelium is disrupted.

Other
The M3 receptors are also located in many glands, both endocrine and exocrine glands, and help to stimulate secretion in salivary glands and other glands of the body.

Other effects are:
 * increased secretions from stomach
 * Eye accommodation

Agonists

 * acetylcholine
 * bethanechol
 * carbachol
 * oxotremorine
 * pilocarpine (in eye)

Antagonists

 * atropine
 * dicycloverine
 * tolterodine
 * oxybutynin
 * ipratropium
 * darifenacin
 * tiotropium