Dopamine receptor D5

Dopamine receptor D5, also known as D1BR, is a protein that in humans is encoded by the DRD5 gene. It belongs to the D1-like receptor family along with the D1 receptor subtype. D5 receptor is a subtype of the dopamine receptor that has a 10-fold higher affinity for dopamine than the D1 subtype. The D5 subtype is a G-protein coupled receptor, which promotes synthesis of cAMP by adenylyl cyclase via activation of Gαs/olf family of G proteins. Both D5 and D1 subtypes activate adenylyl cyclase. D1 receptors were shown to stimulate monophasic dose-dependent accumulation of cAMP in response to dopamine, and the D5 receptors were able to stimulate biphasic accumulation of cAMP under the same conditions, suggesting that D5 receptors may use a different system of secondary messengers than D1 receptors. Activation of D5 receptors is shown to promote expression of brain-derived neurotrophic factor and increase phosphorylation of protein kinase B in rat and mice prefrontal cortex neurons. In vitro, D5 receptors show high constitutive activity that is independent of binding any agonists. D5 receptor is highly homologous to the D1 receptor. Their amino acid sequences are 49% to 80% identical. D5 receptor has a long C-terminus of 93 amino acids, accounting for 26% of the entire protein. In spite of the high degree of homology between D5 and D1 receptors, their c-terminus tails have little similarity. In humans, D5 receptor is encoded on the chromosome 4p15.1–p15.3. The gene lacks introns and encodes a product of 477 amino acids. Two pseudogenes for D5 receptor exist that share 98% sequence with each other and 95% sequence with the functional DRD5 gene. These genes contain several in-frame stop codons that prevent these genes from transcribing a functional protein. D5 receptor is expressed more widely in the CNS than its close structural homolog dopamine receptor D1. It is found in neurons in amygdala, frontal cortex, hippocampus, striatum, thalamus, hypothalamus, basal forebrain, cerebellum, and midbrain. Dopamine receptor D5 is exclusively expressed by large aspiny neurons in neostriatum of primates, which are typically cholinergic interneurons. Within a cell, D5 receptors are found on the membrane of soma and proximal dendrites. They are also sometimes located in the neuropil in the olfactory region, superior colliculus, and cerebellum. D5 receptor is also found in striatal astrocytes of the rat basal ganglia. The receptors of this subtype are also expressed on dendritic cells and T helper cells.