Dopamine receptor D2 (D2L) (D2L)

The Human dopamine D2L receptor is the long isoform of the D2 receptor, a Class A G protein-coupled receptor (GPCR) encoded by the DRD2 gene [5, 10]. It is distinguished from the short isoform (D2S) by a 29-amino acid insertion in the third intracellular loop, which facilitates its primary role as a postsynaptic receptor in the striatum and other brain regions [4, 6]. D2L signaling is mediated through Gi/o proteins, leading to the inhibition of adenylyl cyclase and the modulation of various downstream effectors like DARPP-32 and GIRK channels [4, 8]. This receptor plays a central role in regulating motor control, reward-motivated behavior, and endocrine functions, particularly the inhibition of prolactin release [1, 9]. Dysregulation of D2L-mediated signaling is a hallmark of several neuropsychiatric and neurological disorders, including schizophrenia, where overactivity is linked to positive symptoms, and Parkinson's disease, characterized by a loss of dopaminergic input [11, 12]. Consequently, D2L is a major therapeutic target; antipsychotic drugs typically act as D2L antagonists or partial agonists to alleviate psychosis, while dopamine agonists are used to manage motor symptoms in Parkinson's disease [3, 13]. Therapeutic challenges include managing side effects like extrapyramidal symptoms and hyperprolactinemia, which arise from the receptor's widespread influence on motor and endocrine pathways [12, 14].

Other names

D2RDRD2D2longDopamine D2 receptorD2 dopamine receptorD2L receptor

Drugs targeting the D2L receptor primarily act as antagonists to block postsynaptic signaling in the treatment of schizophrenia and other psychotic disorders, or as agonists to stimulate the receptor and compensate for dopamine deficiency in Parkinson's disease. Partial agonists are also utilized to stabilize dopaminergic activity by acting as functional antagonists in hyper-dopaminergic states and functional agonists in hypo-dopaminergic states.