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Alpha2 Receptor

  • The Alpha2 Adrenergic Receptor is an inhibitory G-protien coupled receptor that binds norepinephrine and is present in both the CNS and sympathetic arm of the autonomic nervous system. Within sympathetic fibers, Alpha2 receptors are uniquely found on the presynaptic terminals of postganglionic sympathetic neurons and serve to attenuate further release of norepinephrine. These receptors appear to be the primary adrenergic receptor within the CNS and the pharmacological effects of alpha2 modulation are most likely the result of actions on these CNS-located alpha2 receptors.
Mechanism of Action
  • The Alpha2 Receptor is a G-protein coupled receptor connected to the Gi G-protein. Once activated by the receptor, Gi serves to inhibit adenylyl cyclase, yielding reduced release of further norepinephrine from the presynaptic terminal. Thus, the alpha2 receptor essentially acts as a major mechanism of negative feedback control during sympathetic outflow as follows: Sympathetic activation leads to release of norepinephrine from the presynaptic terminal which in turn activates presynaptic alpha2 receptors to reduce further presynpatic norepinephrine release.
Physiological Actions
  • Within the autonomic nervous system, the major physiological consequences of alpha2 receptor activity are to limit sympathetic activation. The central actions of alpha2 receptors are still being elucidated. Interestingly, the pharmacological actions of specific alpha2 agonists and antagonists are likely the result of modulating these central receptors rather than those in the peripheral nervous system.