moderately reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle. M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated Ca2+ channels, and increasing efflux of K+, in general, leading to inhibitory-type effects. M3 receptor The M3 muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. Because the M3 receptor is Gq-coupled and mediates an increase in intracellular calcium, it typically causes contraction of smooth muscle, such as that observed during bronchoconstriction and bladder voiding. 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, thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle, M3 mediates vasoconstriction in diseases wherein the vascular endothelium is disrupted. The M3 receptors are also located in many glands, which help to stimulate secretion in, for example, the salivary glands, as well as other glands of the body. Like the M1 muscarinic receptor, M3 receptors are G proteins of class Gq that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. M4 receptor M4 receptors are found in the CNS. M4 receptors work via Gi receptors to decrease cAMP in the cell and, thus, produce generally inhibitory effects. Possible bronchospasm may result if stimulated by muscarinic agonists M5 receptor Location of M5 receptors is not well known. Like the M1 and M3 muscarinic receptor, M5 receptors are coupled with G proteins of class Gq that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. Pharmacological application Ligands targeting the mAChR that are currently approved for clinical use include non-selective antagonists for the treatment of Parkinson's disease, atropine (to dilate the pupil), scopolamine (used to prevent motion sickness), and ipratropium (used in the treatment of COPD). See also Muscarinic agonist Muscarinic antagonist Nicotinic acetylcholine receptor Nicotinic agonist Nicotinic antagonist Vagal escape References External links Acetylcholine Receptors (Muscarinic) Neurochemistry Neurophysiology Acetylcholine receptors