α2 adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. Studies in mice revealed that both the α2A and α2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the α2A subtype inhibited transmitter release at high stimulation frequencies, whereas the α2C subtype modulated neurotransmission at lower levels of nerve activity.
Although the pre-synaptic functions of α2A receptors have been a major focus (see above), the majority of α2 receptors in the brain are actually localized post-synaptically to noradrenergic terminals, and therefore aid in the function of norepinephrine. Many post-synaptic α2A receptors have important effects on brain function; for example, α2A receptors are localized on prefrontal cortical neurons where they regulate higher cognitive function.
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