Dopamine receptor D2 (short isoform) (D2S) (D2S)

The Dopamine receptor D2 (short isoform), commonly known as D2S, is a G protein-coupled receptor (GPCR) that plays a pivotal role in regulating dopaminergic neurotransmission within the central nervous system (UniProt P14416). It is one of two major isoforms encoded by the DRD2 gene, produced through alternative splicing of exon 6, and is distinguished from the long isoform (D2L) by the absence of a 29-amino acid sequence in the third intracellular loop (NCBI Gene ID: 1813). D2S is predominantly localized presynaptically, where it functions as an autoreceptor to provide negative feedback, inhibiting the synthesis and release of dopamine to maintain synaptic homeostasis (PMID: 10446300). This receptor is a primary target for a wide range of pharmacological agents, including antipsychotics used to treat schizophrenia and bipolar disorder, as well as dopamine agonists used for Parkinson's disease (StatPearls: Antipsychotic Medications). Dysregulation of D2S-mediated signaling is linked to various neuropsychiatric conditions and addictive behaviors. However, therapeutic targeting is often complicated by the receptor's involvement in the tuberoinfundibular and nigrostriatal pathways, leading to side effects such as hyperprolactinemia and extrapyramidal symptoms (PMID: 21945130).

Other names

D2S receptorDRD2SDopamine D2S receptorD2 short isoformD2 receptor short form

Drugs targeting the Dopamine receptor D2 (short isoform) act through several mechanisms: typical and atypical antipsychotics function as antagonists or partial agonists to reduce overactive dopaminergic signaling in the mesolimbic pathway; dopamine agonists (e.g., pramipexole) stimulate the receptor to treat Parkinson's disease; and partial agonists (e.g., aripiprazole) provide a stabilizing effect by acting as an agonist in low-dopamine states and an antagonist in high-dopamine states (StatPearls: Antipsychotic Medications; PMID: 10446300).