DRD5

DRD5 Full Name

dopamine receptor D5

DRD5 Introduction

The D5 receptor is a subtype of dopamine receptor, which has a 10 fold higher affinity for dopamine than the D1 subtype. Dopamine receptor D5, also known as D1BR, is a protein encoded by the DRD5 gene in humans. It belongs to the D1 like receptor family along with the D1 receptor subtype. The D1 receptor has been shown to stimulate monophasic dose-dependent accumulation of cAMP in dopamine, while the D5 receptor can stimulate biphasic accumulation of cAMP under the same conditions, indicating that the D5 receptor may use a different secondary messenger system than the D1 receptor. D5 subtype is a G protein coupled receptor that promotes the synthesis of cAMP by adenylate cyclase by activating G proteins of the G α s/olf family. Both D5 and D1 subtypes activate adenylate cyclase.

Figure. Heterogeneous dopamine receptor signaling complexes and their association with diseases.(Source: Perreault ML, et al, 2014)

Primary Structure and Chromosome Location
In humans, the D5 receptor is encoded on chromosomes 4p15.1-p15.3. This gene lacks introns and encodes a product of 477 amino acids. There are two D5 receptor pseudogenes that share 98% of their sequence with each other and 95% with the functional DRD5 gene. These genes contain several stop codons within the frame that prevent them from transcribing functional proteins. The D5 receptor is highly homologous to the D1 receptor. Their amino acid sequences share 49% to 80% similarity. The D5 receptor has a long C-terminus of 93 amino acids, accounting for 26% of the entire protein. Although there is a high degree of homology between D5 and D1 receptors, their c-terminal tails have almost no similarity.

Clinical Significance
The D5 receptor is involved in synaptic processes of learning and memory. These receptors are involved in the formation of striatal LTD in rodents, which is opposite to the involvement of D1 receptors in the formation of LTP in the same brain region. The D5 receptor is also associated with the consolidation of fear memories in the amygdala. Research has shown that M1 muscarinic receptors work synergistically with D5 receptors and β 2 adrenergic receptors to consolidate induced fear memories. This indicates that these G protein coupled receptors redundantly activate phospholipase C in the basolateral amygdala. One effect of phospholipase C activation is the inactivation of KCNQ channels. Due to the conduction of M current through KCNQ channels, the threshold of action potential is increased, and therefore the inactivation of these channels leads to increased neuronal excitability and enhanced memory consolidation.

Alternate Names for DRD5

DRD5; dopamine receptor D5; DBDR; DRD1B; DRD1L2; D(1B) dopamine receptor; dopamine D5 receptor; dopamine receptor D1B; d(5) dopamine receptor; D1beta dopamine receptor;

• 1.Perreault ML, Hasbi A, O'dowd BF, George SR. Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology. 2014, 39(1):156-68.