D1like receptors

The dopamine Di receptor The gene encoding the dopamine D1 receptor was cloned in the early 1990s by four independent laboratories (Dearry et al. 1990; Monsma et al. 1990; Sunahara etal. 1990; Zhou etal. 1990). It was identified in several species, including opossum, goldfish, tilapia, frog, chicken, and Drosophila (see Neve and Neve 1997). The mammalian D1 receptor consists of a 446-amino acid protein with a Mr ~49,000, and strong sequence homology among different species. For example, the human and rhesus D1 receptors differ by only two amino acid residues (Machida et al. 1992).

The rat dopamine Di receptor gene is approximately 4kb in size, consisting of two exons separated by a 115-bp intron (Zhou et al. 1992). However, since the intron is in the 5'-untranslated region, the rat dopamine D1 receptor is virtually intronless. The human dopamine D1 receptor gene is located on the long arm of chromosome 5, at q35.1 (Grandy etal. 1990) and has a similar organization, with very minor differences (Minowa etal. 1992). All the mammalian D1 receptors have several potential sites for N-linked glycosylation and phosphorylation. For the human D1 receptor, these include Asn-5 at the amino terminus and Asn-175 in the third extracellular domain for glycosylation. Potential phosphorylation by PKAmay occur on Thr-136 in the second cytoplasmic loop and Thr-268 at the C-terminal end of the third cytoplasmic loop, while multiple serine and threonine residues found in the long cytoplasmic tail of mammalian D1 receptors represent potential sites of phosphorylation by G protein-coupled receptor kinases.

The dopamine D5 receptor The first description of the cloning of the human dopamine D5 receptor gene was published in 1991 (Sunahara etal. 1991). The human D5 receptor was isolated by using sequences derived from the D1 dopamine receptor (Sunahara et al. 1991; Grandy et al. 1991) to probe genomic libraries. Hence the D5 receptor sequence was found to be more closely related to the D1 receptor than to the D2-like dopamine receptors. In addition to the human dopamine D5 receptor, the rat (Tiberi et al. 1991), and the chicken (Demchyshyn et al. 1995) D5 receptor genes have also been cloned. The human dopamine D5 receptor gene was localized to the short arm of chromosome 4 (Polymeropoulos et al. 1991) and, like the dopamine D1 gene, contains no introns within its coding region (Tiberi etal. 1991; Sunahara etal. 1991).

The human dopamine D5 receptor is 477-amino acids in length, sharing ~60% amino acid identity with the D1 receptor, while the rat D5 receptor has ~83% amino acid sequence homology with the human D5 receptor. At least two potential sites for N-linked glycosylation (Asn-7 and Asn-199) and two potential sites for phosphorylation by PKA (Thr-153 and Ser-260) are found in the human D5 receptor.

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