alpha2A

Alpha-2A refers to the alpha-2A adrenergic receptor, one of the three alpha-2 adrenergic receptor subtypes. In humans it is encoded by the ADRA2A gene, located on chromosome 10. The receptor is a G protein-coupled receptor that primarily couples to Gi/o proteins, leading to inhibition of adenylate cyclase, reduced cAMP levels, and downstream effects such as opening potassium channels and inhibiting calcium influx.

Distribution and function vary by tissue. The alpha-2A receptor is expressed in the central and peripheral nervous systems, with notable presence in the locus coeruleus and related autonomic networks, as well as on platelets and certain peripheral tissues. In presynaptic neurons, alpha-2A receptors provide negative feedback to inhibit norepinephrine release, helping regulate sympathetic tone. In the central nervous system, activation can modulate arousal, attention, sedation, and stress responses, and it contributes to analgesia and anxiolysis under certain pharmacological conditions.

Pharmacology and clinical relevance are dominated by agents that target this receptor. Endogenous ligands include norepinephrine and epinephrine. Clinically important agonists include dexmedetomidine, which is relatively selective for the alpha-2A subtype and is used for sedation; clonidine and guanabenz are less selective but also activate alpha-2 receptors. Antagonists such as yohimbine can reverse alpha-2–mediated effects. Variation in the ADRA2A gene has been studied for potential influences on drug response and certain physiological traits, though findings are complex and ongoing.

See also: adrenergic receptor, ADRA2A gene, clonidine, dexmedetomidine.

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