Dog Dopamine Receptor D2 (DRD2) Protein

Background

DRD2 is a G protein-coupled receptor belonging to the D2-like receptor family and is highly expressed in the striatum, substantia nigra, and hypothalamus, where it regulates motor control, reward processing, and endocrine function. DRD2 primarily couples to Gi/o proteins, which inhibit adenylate cyclase, reducing cyclic AMP (cAMP) levels and modulating downstream signaling pathways. It exists in two isoforms: the short form (D2S), which functions presynaptically to inhibit dopamine release, and the long form (D2L), which mediates postsynaptic signaling. DRD2 plays a key role in motor control, and its dysfunction is closely linked to Parkinson’s disease, where loss of dopaminergic neurons leads to motor deficits. In neuropsychiatric disorders, DRD2 dysregulation contributes to schizophrenia, bipolar disorder, and drug addiction, where abnormal dopamine signaling disrupts cognition, behavior, and reward mechanisms. Antipsychotic drugs primarily target DRD2 to alleviate symptoms of psychosis by blocking receptor activity. DRD2 also regulates prolactin secretion from the pituitary gland, and its antagonism can cause hyperprolactinemia. Beyond the CNS, DRD2 influences cardiovascular and gastrointestinal function. Given its central role in motor control, reward signaling, and neuropsychiatric disorders, DRD2 remains a critical therapeutic target for Parkinson’s disease, schizophrenia, and substance abuse.