Alpha-2 adrenergic receptor
protein family
The alpha-2 (α2) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three homologous subtypes, α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.
Cellular localization
The α2A adrenergic receptor is localised in the following central nervous system (CNS) structures:
Brainstem (especially the locus coeruleus as presynaptic & somatodendritic autoreceptor )
Midbrain
Hypothalamus
Olfactory system
Hippocampus
Spinal cord
Cerebral cortex
Cerebellum
Septum
Whereas the α2B adrenergic receptor is localised in the following CNS structures:
Thalamus
Stratum pyramidale of the hippocampus
Cerebellar Purkinje layer
The α2C adrenergic receptor is localised in the following CNS structures:
Midbrain
Thalamus
Amygdala
Dorsal root ganglia
Olfactory system
Hippocampus
Cerebral cortex
Basal ganglia
Substantia nigra
Ventral tegmentum
Effects
The α2-adrenergic receptor is classically located on vascular prejunctional terminals where it inhibits the release of norepinpehrine (noradrenaline) in a form of negative feedback. It is also located on the vascular smooth muscle cells of certain blood vessels, such as those found in skin arterioles or on veins, where it sits alongside the more plentiful α1-adrenergic receptor. The α2-adrenergic receptor binds both norepinephrine released by sympathetic postganglionic fibers and epinephrine (adrenaline) released by the adrenal medulla, binding norepinephrine with slightly higher affinity. It has several general functions in common with the α1-adrenergic receptor, but also has specific effects of its own. Agonists (activators) of the α2-adrenergic receptor are frequently used in anaesthesia where they affect sedation, muscle relaxation and analgesia through effects on the central nervous system (CNS).
In the brain, α2-adrenergic receptors can be localized either pre- or post-synaptically, however the majority of receptors appear to be post-synaptic.
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