Dopamine receptor D2 short isoform (DRD2S)

The **dopamine receptor D2 short isoform (D2S)** is a G protein-coupled receptor (GPCR) and one of the two main isoforms of the dopamine receptor D2, generated by alternative splicing of the DRD2 gene[2][4][5]. D2S acts primarily as a pre-synaptic autoreceptor, modulating dopamine synthesis, storage, and release via inhibitory G proteins (G\(_{i/o}\)), which inhibit adenylyl cyclase and decrease intracellular cAMP levels[2][10]. The D2S receptor is highly expressed in dopaminergic areas like the striatum and acts as a key regulator of dopaminergic neurotransmission[2][10]. It is a critical pharmacological target for antipsychotic drugs (which act as antagonists/partial agonists)[6], and for dopaminergic agonists used in the treatment of Parkinson’s disease and pituitary adenomas[4][6]. Dysregulation or abnormal signaling through the D2S receptor is implicated in psychiatric and movement disorders. Both the short (D2S) and long (D2L) isoforms share similar pharmacology but have distinct cellular distributions and functions: D2S is primarily pre-synaptic (autoreceptor), while D2L is primarily post-synaptic[2].

Other names

Dopamine D2S receptorD2SDopamine receptor D2 short formD2 short isoformDRD2 shortD2Sh

Antagonism (blockade) at D2 receptor (major mechanism for antipsychotics) Partial agonism at D2 receptor (for some atypical antipsychotics) Agonism at D2 receptor (dopaminergic stimulants for Parkinson’s disease) Modulation of pre-synaptic (D2S autoreceptor) activity to reduce dopamine synthesis/release