Cholinergic receptors are proteins on cell surfaces that respond to the molecule acetylcholine. Acetylcholine is a neurotransmitter that carries signals between nerve cells and other cells, like muscles or glands. The interaction between acetylcholine and its receptors facilitates a wide array of bodily functions, from muscle movement to memory formation. These receptors are broadly distributed, playing a part in the somatic and autonomic nervous systems.
Nicotinic Receptors
The first major class, nicotinic receptors, is named after nicotine because the stimulant also activates them. These are ligand-gated ion channels. When acetylcholine binds to the receptor, it changes the protein’s shape, opening a channel for positive ions like sodium and potassium to enter the cell. This rapid influx of positive ions excites the cell, causing it to generate an electrical signal.
One of the most well-known locations for nicotinic receptors is the neuromuscular junction, where nerves connect to skeletal muscles. When a nerve releases acetylcholine here, it binds to nicotinic receptors on the muscle fiber, causing it to contract almost instantaneously. This process allows for voluntary movement.
Beyond muscle control, nicotinic receptors are found in the autonomic ganglia, which are clusters of nerve cells that act as relay stations for the sympathetic and parasympathetic nervous systems. Here, they transmit signals that regulate involuntary bodily functions. Nicotinic receptors are also present in the central nervous system, where they are involved in cognitive functions like learning and memory.
Muscarinic Receptors
The second category, muscarinic receptors, is named for muscarine, a substance from certain mushrooms that activates these sites. Unlike nicotinic receptors, they operate through a slower mechanism and belong to a family of proteins called G-protein coupled receptors (GPCRs). When acetylcholine binds to a muscarinic receptor, it does not open an ion channel directly.
Instead, the activated receptor engages a G-protein, which initiates biochemical reactions that produce the cell’s response. This process is more prolonged and can result in varied effects, including changes to ion channels, enzymes, or gene expression. The response can be either excitatory or inhibitory, depending on the receptor subtype and cell type.
Muscarinic receptors are predominantly found in organs stimulated by the parasympathetic nervous system, which governs “rest and digest” functions. For example, their activation by acetylcholine slows the heart rate. In the smooth muscles of the digestive tract and lungs, they promote contraction, while also stimulating glands to increase secretions like saliva. There are five main subtypes (M1-M5) distributed throughout different tissues, including the central nervous system.
Clinical Significance and Drug Interactions
The distinct locations and mechanisms of nicotinic and muscarinic receptors make them targets for many drugs and toxins. For instance, some Alzheimer’s medications work by inhibiting the enzyme that breaks down acetylcholine. This increases its availability to stimulate cholinergic receptors in the brain, potentially improving cognitive function. Conversely, blocking these receptors has therapeutic uses, such as the drug atropine, which blocks muscarinic receptors to increase a slow heart rate or reduce saliva production during surgery.
The autoimmune disease myasthenia gravis is a clear example of receptor dysfunction. The body’s immune system attacks and destroys nicotinic receptors at the neuromuscular junction, leading to severe muscle weakness. The effects of certain poisons also highlight the clinical relevance of these receptors. Nerve agents, for example, prevent the breakdown of acetylcholine, causing massive overstimulation of both receptor types and leading to systemic failure, including convulsions and paralysis.