Presynaptic surface receptors of cholinergic neurons

Presynaptic surface receptors of cholinergic neurons are a heterogeneous group of proteins located on the terminal membrane of neurons that synthesize and release acetylcholine (ACh). These receptors play a vital role in the autoregulation of neurotransmission, providing feedback mechanisms that either inhibit or facilitate the further release of ACh into the synaptic cleft. Key members of this group include muscarinic autoreceptors (primarily M2 and M4 subtypes) and various nicotinic acetylcholine receptor (nAChR) subtypes. Additionally, this category includes specific surface proteins such as Synaptic Vesicle Glycoprotein 2 (SV2) and Synaptotagmin, which serve as high-affinity receptors for Botulinum neurotoxins (BoNTs). These receptors are the primary therapeutic targets for Botulinum toxin products, which are used to treat conditions characterized by cholinergic overactivity, such as muscle spasticity, dystonia, and hyperhidrosis. Pharmacological modulation of these receptors is also explored in the context of neurodegenerative diseases and cognitive enhancement.

Other names

Presynaptic cholinergic receptorsCholinergic autoreceptorsBotulinum toxin receptorsPresynaptic muscarinic receptorsPresynaptic nicotinic receptors

Drugs targeting these receptors primarily modulate the release of acetylcholine. Botulinum toxins bind to these receptors to enter the neuron and cleave SNARE proteins, thereby inhibiting acetylcholine release and causing muscle paralysis. Agonists or antagonists of presynaptic autoreceptors (like M2/M4) modulate the feedback loops that control the amount of acetylcholine in the synaptic cleft.