Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes.

Abstract

The dopamine receptors are integral membrane proteins that interact with guanine nucleotide-binding proteins (G proteins) to transduce dopamine stimulation into intracellular responses. The majority of dopamine receptors are concentrated in the mesocortico-mesolimbic, nigrostriatal, and tuberoinfundibular pathways. These neuronal circuits are known to influence mood, behavior, initiation of movement, and prolactin secretion. Prior to the cloning of the rat D2 dopamine receptor gene (1) only D1 and D2 receptors were generally acknowledged to account for the diverse physiological effects of dopamine (2-4), although some pharmacological evidence was inconsistent with this view (5).With nucleic acid probes based on the sequence of the cloned rat D2 receptor gene it was quickly revealed that at least four dopamine receptor genes exist in humans and rats (6-15). Based on their genomic organization these genes can be divided into two types: those with (D2, D3, and D4) and those without (D1) introns in their coding regions. During a structural analysis of the human D1 dopamine receptor gene we obtained evidence that the human genome contains a sequence that is similar but not identical to the D1 gene. To determine whether or not this sequence encoded a dopamine receptor, we undertook its cloning and characterization

A primordial dopamine D1‐like adenylyl cyclase‐linked receptor from Drosophila melanogaster displaying poor affinity for benzazepines

“…The single letter amino acid code is used. Sequences sources are as follows: human DI [31,53,54], monkey D1 [55], rat D1A [53], opposum D1A [56], goldfish D1 [57], Xen D1A, D1B and D1C [6], human D5 [29,58,59], rat D1B [60], chicken D1A, D1B, DID [7]. receptors; and 49% to human D5 and chicken DIB receptors.…”

D1/D5 Dopamine Receptors Stimulate Intracellular Calcium Release in Primary Cultures of Neocortical and Hippocampal Neurons

“…Heterologously expressed D1/D5 DA receptors typically stimulate G s (Grandy et al 1991;Zhou et al 1990) resulting in cAMP accumulation. Yet the pharmacology of the responses we detect clearly indicates that endogenous D1-like DA receptor signaling also results in increased Ca i 2ϩ levels.…”

“…Agonist stimulation of recombinant D1 and D5 DA receptors in heterologous systems results in cyclic 3Ј-5Ј AMP (cAMP) accumulation due to coupling with the heterotrimeric G protein ␣ subunit, G s (Grandy et al 1991;Zhou et al 1990). Additionally, in neurons derived from dorsal striatum, D1/D5 receptor agonists regulate Ca 2ϩ channel activity via a signaling cascade including cAMP-dependent kinase (PKA), DARPP-32, and protein phosphatase I (Surmeier et al 1995).…”

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

“…On the basis of their structural, pharmacological, and biochemical properties, these receptors were classified as either 184 D1-class dopamine receptors [D1 and D5 (originally identified as D1B) (Tiberi et al, 1991)] or D2-class dopamine receptors (D2, D3, and D4) (Andersen et al, 1990;Niznik and Van Tol, 1992;Sibley and Monsma, 1992;Sokoloff et al, 1992a;Civelli et al, 1993;Vallone et al, 2000). In addition to these functional receptors, two pseudogenes have been described for the human D5 dopamine receptor that encodes truncated nonfunctional receptor forms (Grandy et al, 1991).…”