cholinergic

Cholinergic refers to neurons, tissues, or actions that involve acetylcholine (ACh) as a neurotransmitter or chemical mediator. The cholinergic system operates through two main receptor types: nicotinic receptors, which are ligand-gated ion channels, and muscarinic receptors, which are G protein–coupled receptors. Cholinergic neurons are present in the peripheral nervous system, including the parasympathetic nervous system and the neuromuscular junction, as well as in various brain regions where they influence cognitive and arousal states.

Acetylcholine is synthesized in cholinergic neurons by the enzyme choline acetyltransferase (ChAT) from acetyl-CoA and choline. The transmitter is packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT) and released into the synapse in response to an action potential. After receptor activation, acetylcholine is rapidly inactivated by acetylcholinesterase into choline and acetate, with choline subsequently recycled by the presynaptic membrane via the high-affinity choline transporter.

Nicotinic receptors are primarily associated with fast synaptic transmission at the neuromuscular junction and in certain central synapses, whereas muscarinic receptors modulate a variety of autonomic and CNS functions. In the periphery, acetylcholine binding to muscarinic receptors mediates parasympathetic effects such as slowed heart rate, increased glandular secretion, and smooth muscle stimulation. In the CNS, cholinergic signaling supports attention, learning, and memory, and degeneration of basal forebrain cholinergic neurons is a hallmark of Alzheimer’s disease.

Pharmacologically, the cholinergic system is targeted by acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine) used in dementia, muscarinic agonists (e.g., bethanechol, pilocarpine) for specific conditions, and nicotinic agents (e.g., nicotine, varenicline). Anticholinergic drugs (e.g., atropine, ipratropium) block muscarinic signaling. Overstimulation can cause cholinergic toxicity, with symptoms such as salivation, lacrimation, urination, defecation, GI upset, emesis, and miosis, known as SLUDGE.