Dopamine D1-like receptor (D1-like receptor) (D1-like receptor)

Dopamine D1-like receptors, comprising the D1 and D5 subtypes, are G protein-coupled receptors primarily located in the central nervous system, particularly within the striatum, cerebral cortex, and hypothalamus (UniProt, 2024). These receptors are characterized by their ability to stimulate adenylyl cyclase activity upon binding with dopamine, leading to increased intracellular cAMP levels and subsequent downstream signaling that modulates neuronal excitability and synaptic plasticity (StatPearls, 2023). In the treatment of Parkinson's disease, levodopa serves as a metabolic precursor that is converted into dopamine by aromatic L-amino acid decarboxylase. This exogenous dopamine then activates D1-like receptors on the GABAergic medium spiny neurons of the direct pathway in the basal ganglia. This activation helps compensate for the loss of endogenous dopaminergic signaling, thereby improving motor symptoms such as bradykinesia and rigidity (NIH, 2023). However, chronic stimulation of these receptors, especially with fluctuating levels of levodopa-derived dopamine, can lead to complications such as dyskinesia and psychiatric side effects like hallucinations or impulse control disorders (PubMed, 2022).

Other names

D1 receptorD5 receptorDRD1DRD5D1-like dopamine receptorDopamine receptor D1Dopamine receptor D5

Dopamine D1-like receptors (D1 and D5) are coupled to the Gs/olf protein, which stimulates adenylyl cyclase, increasing intracellular cyclic AMP (cAMP) levels and activating protein kinase A (PKA) (StatPearls, 2023). In the context of Parkinson's disease, dopamine derived from exogenous levodopa stimulates these receptors in the striatum to facilitate the 'direct pathway' of the basal ganglia, which promotes voluntary movement and counteracts the inhibitory effects of dopamine depletion (PubMed, 2021).