D2 (Dopamine) Receptors



D2 receptors are dopamine receptors primarily located in the brain. Dopamine binding to D2 receptors activates a Gi protein subunit, which decreases downstream cAMP levels. Functionally, D2 receptors play a role in the control of motor function by mediating the indirect pathway between the basal ganglia. D2 receptor signalling also inhibits prolactin, which is relevant since D2 antagonizing drugs can elevate prolactin levels to cause gynecomastia and galactorrhea. D2 agonists are used to treat Parkinson disease, while D2 antagonists are used to treat mood disorders including schizophrenia and psychosis.

Key Points

  • D2 Receptors
    • GPCR that binds dopamine
      • Activates a Gi subunit
        • Inactivates adenylyl cyclase and cAMP second messenger cascade
    • Locations
      • Basal ganglia (substantia nigra)
      • Pituitary gland
      • CNS
    • Actions
      • Motor Control
        • Via modulation at basal ganglia
        • D2 agonists used in the treatment of Parkinson’s disease
      • Role in psychotic disorders
        • Involved in schizophrenia and acute psychosis
        • D2 antagonists used as antipsychotic agents
      • Inhibits prolactin release
        • D2 signaling inhibits lactotrophs of the anterior pituitary gland
        • Hyperprolactinemia may be seen with D2 antagonists