Dopamine D1 receptor; Dopamine D2 receptor, short isoform (D1R; D2S)

Dopamine D1 and D2S receptors are members of the G protein-coupled receptor family expressed primarily in the central nervous system. The D1 receptor couples to Gs proteins and stimulates adenylyl cyclase, increasing cAMP, while the D2S isoform couples to Gi proteins and inhibits adenylyl cyclase, reducing cAMP. D1 and D2 receptors are essential for fine-tuning neuronal activity and synaptic signaling involved in motor control, cognition, emotion, and motivation. These receptors are key drug targets in the treatment of Parkinson's disease, schizophrenia, and other neuropsychiatric conditions. Their distinct structural, signaling, and pharmacological properties underlie the development of both selective and non-selective therapeutic agents, as well as the mechanisms by which dopaminergic dysregulation contributes to disease. The D2 receptor exists in two isoforms (D2S-short and D2L-long) created by alternative splicing, with distinct regional and subcellular expression.

Other names

D1 receptor (D1R)D2-short receptor (D2S)Dopamine receptor subtypesD1-like dopamine receptorD2-like dopamine receptor

Agonists: Activation of receptor stimulates/inhibits adenylyl cyclase via G protein coupling (D1: Gs increases cAMP; D2S: Gi decreases cAMP) Antagonists: Block dopamine signaling Partial agonists: Modulate signaling in a context-dependent manner Biased ligands: Preferentially activate selected intracellular signaling pathways