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Concept
Alpha-5 nicotinic acetylcholine receptor
Summary
The alpha-5 nicotinic acetylcholine receptor (α5 nAChR) also known as the α5 receptor is a type of ligand gated nicotinic acetylcholine receptor involved in pain regulation. One of the 5 transmembrane subunits of this receptor is the α5 subunit and is transcribed by the CHRNA5 gene. This receptor is commonly associated with nicotine addiction, immunotherapy, cancer, pain and attention.
There are two major classes of acetylcholine receptors: nicotinic receptors, which bind to exogenous nicotine, and muscarinic receptors, which bind exogenous muscarine. Nicotinic acetylcholine receptors (nAChRs) were initially discovered through the application and binding of nicotine, however, endogenous acetylcholine is the ligand that binds under normal physiological conditions. The nAChRs are single channel ionotropic receptors found throughout the brain and body that allow for cations to flow in and out of cells. These receptors consist of five transmembrane subunits with the α5 nAChR defined by the presence of the α5 subunit. The α5 nAChR is located in various areas of the brain including the cortex, hippocampus, hypothalamus, inferior colliculus, medial habenula, olfactory bulb and striatum. The α5 nAChR is involved in modulating chronic inflammation and peripheral nerve injury.
Acetylcholine binds in the cortex, hippocampus, hypothalamus, inferior colliculus, striatum and olfactory bulb. CHRNA5 is located in a gene cluster on chromosome 15q24 along with CHRNA3 and CHRNB4. Homopentameric receptors with five acetylcholine binding sites contain two a-subunits (a2-a4 or a6) and two non-a-subunits (B2 or B4). Alpha5 subunits tend to be the fifth that does not directly bind to acetylcholine and act as auxiliary subunits. Rather, they may be important for receptor targeting and localization on the cell membrane. The alpha subunits normally assemble into both alpha3B4-containing and alpha4-beta2 containing nAChR assemblies. These receptors have been found on dopaminergic neurons in the rodent striatum and are involved in DA release upon nicotine stimulation.
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