Nicotinic Acetylcholine Receptors in Health and Disease
Neurotoxins
Ronald J. Lukas, Ph.D., Director
Some neurotoxins have the potential to act on nicotinic acetylcholine receptors. For example, neurotoxic proteins found in the venom of poisonous snakes such as cobras (illustrated here), kraits, mambas, and sea snakes target nicotinic receptors in mammalian muscle and some nicotinic receptors in the nervous system. These toxins literally cover up the acetylcholine or nicotine binding sites on receptors, preventing acetylcholine or nicotine from triggering the ion channel to open.
In the wild, when such toxins are delivered to a mammal, they diffuse to the diaphragm. Once there, they block nicotinic receptors that receive chemical signals from the phrenic nerve that would normally promote breathing. The prey is immobilized and eventually dies from asphyxiation. In a laboratory setting, these toxins are valuable tools for the study of nicotinic receptors.
Other toxins (e.g. from frogs, algae, or sea snails) also can be used to study nicotinic receptors. In fact, nicotine itself is a toxic substance and seems to have evolved as a natural insecticide.
The wide distribution and critical physiological roles of nicotinic acetylcholine receptors make them ideal targets in the attempt to modify brain and body functions pharmacologically. Not surprisingly, nicotinic receptors are targeted by a variety of toxins and bioactive substances. Consequently, these receptors are the subject of intensive investigations that seek to identify new medicines for use in treating neurological and/or psychiatric disorders, along with other diseases that strike outside the nervous system.
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