Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. It is a small-molecule neurotransmitter and neuromodulator with roles in the peripheral and central nervous systems and is associated with the sympathetic and parasympathetic components of the autonomic nervous system.  ACh is also the main signal used by motor neurons to activate smooth muscle and, more recently, has been shown to play an important part in signaling from the nervous system to the immune system. ACh is typically released from presynaptic terminals into the synaptic cleft of neurons for transmission of the signal to acetylcholine receptors (AChRs) on the post-synaptic cell. 
ACh binds to two subclasses of AChR: nicotinic and muscarinic AChRs, which are historically distinguished by their ability to bind either nicotine or muscarine (natural but nonendogenous agonists). ACh signaling is also regulated by the enzyme acetylcholine esterase [AChE (butylChE present in plasma)] which is present within the synaptic cleft or neuromuscular junctions and catalyzes the hydrolysis of ACh into acetate and choline. This neurotransmitter/modulator, in many instances, works locally at close range (synaptic clefts), but the cholinergic tone of its receptors (propensity to signal) can be regulated by endogenous levels of acetylcholine or exogenous ligands


1.VanPatten S,et al. Drug Discov Today. 2017 Jan;22(1):97-104.