Acetylcholine Receptor Subtypes

There are two broadly different acetylcholine receptors: muscarinic and nicotinic acetylcholine receptors. They are named after the major chemical that stimulates each of them: Acetylcholine stimulates both receptors while muscarine stimulates only muscarinic[1] acetylcholine receptors, and nicotine stimulates nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are located at multiple sites. These include the entire ganglion in the sympathetic and parasympathetic nervous system, the adrenal medulla and the sweat glands, which are also part of the sympathetic nervous system, and finally at the neuromuscular junction of the somatic nervous system. Muscarinic acetylcholine receptors are located at the end organ sites of the parasympathetic nervous system, such as the smooth muscles of the gastrointestinal tract, bladder, heart, and blood vessels.

Each of these two acetylcholine receptors has several subtypes, whose functions vary in response to stimulation from acetylcholine. Each receptor subtype responds to different chemicals as well as to acetylcholine, and either nicotine or muscarine (hence the name nicotinic receptor and muscarinic receptor). These receptors are further classified by subtypes in a very complex manner that allows for further sub-specialization. For nicotine, there are two broad subtypes: neuronal-type and muscle-type. They are further subdivided by their molecular make-up and their genetic similarities. Some are located only in the brain, some in the autonomic ganglia, and others only at the neuromuscular junction, the point at which the somatic nerves terminate on skeletal muscle. In total, nicotinic receptors contain 4 subfamilies comprising 17 subunits. This further sub-specialization allows the nicotinic receptor subtypes to differ in their response to various chemicals at muscle tissues and nervous tissues. Many of the historical toxins from plants and animals act on either the muscarinic receptor types, such as atropine from the deadly nightshade, or the nicotinic receptor types, such as curare (found on the skin of frogs and used in poison darts), and alpha-bungarotoxin[2] (found in snake venom), which act at the neuromuscular junction leading to paralysis. Figure 6 shows the nicotine receptor.

Central Nervous System (CNS)

Acetylcholine's role is also multiple in the CNS. It principally acts as a neuromodulator[3], which means that it affects many other neurotransmitter systems to coordinate their activity as

An enzyme that breaks down acetylcholine, rendering it inactive. Blocking this enzyme leads to a relative increase in acetylcholine.

A schematic illustration of an Acetylcholine Receptor

Figure 6 A schematic illustration of an Acetylcholine Receptor

Illustration by Giovanni Maki. © 2004Tabitha M. Powledge. (PLoS Biol. 2004 November; 2(11): e404. Published online 2004 November 16. doi: 10.1371/journal.pbio.0020404.)

well. It plays a very important role in attention, learning, and memory. Many areas of the brain are involved in learning and memory. Patients with Alzheimer's disease lose acetylcholine nerves at a faster rate than normal, partly explaining the loss of learning and memory as a symptom of the disease. Any chemical that can pass into the brain and block acetylcholine receptors (known as an anticholinergic[4]) therefore can negatively impact learning and memory. Many of the new medications for Alzheimer's disease work by blocking the enzyme responsible for breaking down acetylcholine, known as acetylcholinesterase. These acetylcholinesterase inhibitors cause an increase in the amount of acetylcholine and thus improve learning and memory. Acetylcholine also modulates the experience of pain and pleasure in the centers of the brain, known as the limbic areas[5]. Clearly, there is a strong link between these centers, our emotional life, and the memory centers because the strongest memories are usually elicited by strong emotions linked to pleasure and pain. Because the limbic area is the area of pleasure, this is predominantly part of the "reward system" of the brain. Acetylcholine nicotinic receptors act in this area to modulate another neurotransmitter—dopamine[6]—which appears to play an important role in addiction, in addition to its role in attention and alertness.

Finally, acetylcholine plays a role in appetite regulation, particularly in areas of the brain such as the hypothalamus[7], which is one of the principle centers acting to regulate appetite. Nicotinic acetylcholine stimulation suppresses appetite. Many anticholinergic medications have the opposite effect and can stimulate appetite. (Question 91 has more information about the link between nicotine and appetite.)

  • [1] Referring to muscarine, a chemical that stimulates acetylcholine receptors, located in the brain and the parasympathetic nervous system.
  • [2] A snake venom that binds irreversibly to nicotinic acetylcholine receptors at the neuromuscular junction, causing paralysis and death.
  • [3] A process in which one neuron uses different neurotransmitters to connect to several neurons, as opposed to direct synaptic transmission where one neuron directly reaches another neuron.
  • [4] A substance that blocks the effects of acetylcholine in the nervous system.
  • [5] A set of brain structures that includes the hippocampus, amygdala, and anterior thalamic nuclei that support a variety of functions including emotion, behavior, and long- term memory. These structures are closely associated with the olfactory structures.
  • [6] One of the brain's major neurotransmitters, dopamine is responsible for attention, alertness, decision making, reward, pleasure, and elevated mood.
  • [7] Located below the thalamus, just above the brain stem, this part of the brain links the nervous system to the endocrine system via the pituitary gland.
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