title: Adenosine receptors: protein and gene structure.
abstract: Adenosine produces a wide variety of effects throughout the body via activation of cell surface adenosine receptors. Adenosine receptors belong to the family of seven transmembrane domain G protein-coupled receptors and four subtypes have been cloned from a variety of species: the A1AR, A2aAR, A2bAR and A3AR. With a knowledge of both the protein sequence of adenosine receptors and the structure of the A1AR gene, the function and regulation of these receptors can be further explored. Site-directed mutagenesis of the A1AR has resulted in the identification of amino acid residues in transmembrane domains 6 and 7 that are critical in both agonist and antagonist binding. The construction and analysis of A1/A3 chimeric receptors has also revealed regions of adenosine receptors important in ligand binding. These include the distal region of the second extracellular loop of adenosine receptors, which has a role in the binding of both agonist and antagonist ligands. A segment of the exofacial portion of the transmembrane domain 5 of adenosine receptors appears to be involved in the selective recognition of agonist ligands containing a substitution at the 5'-position of the ribose moiety. Isolation of the genomic sequence of the human A1AR, in combination with analysis of the transcript distribution in several tissues, indicates that alternative splicing of the human A1AR occurs in the 5'-untranslated region of the gene. Two distinct transcripts, containing either exons 3, 5 and 6 or exons 4, 5 and 6, exist with exons 3 and 4 apparently mutually exclusive. The exon 4, 5 and 6 transcript has been detected in all tissues that express the A1AR, while the exon 3, 5 and 6 mRNA is found in tissues that display a relatively high A1AR expression. Findings suggest that the presence of two ATG codons in exon 4, upstream of the translation start site, is involved in the repression of the A1AR expression in those tissues containing the exon 4, 5 and 6 transcript.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Olah
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.forename: G L
authors.initials: GL
authors.lastname: Stiles
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D005091:Exons; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D011869:Radioligand Assay; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000737:chemistry* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D018047:Receptors, Purinergic P1; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins