Cloning and characterization of a pharmacologically distinct A 1 adenosine receptor from guinea pig brain

• Published in: Brain research. Molecular brain research. Vol. 26; no. 1; pp. 143 - 155
• Main Authors: Xie, Fan Meng Guo-xi, Chalmers, Derek, Morgan, Caurnel, Watson, Stanley J., Akil, Huda
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 1994
• Subjects: G protein-coupled receptor; In situ hybridization; Mammalian cell expression; Polymerase chain reaction; Radioligand binding; G protein-coupled receptor; Polymerase chain reaction; Mammalian cell expression; Radioligand binding; In situ hybridization
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/0169-328X(94)90085-X

Three full-length cDNA clones encoding the guinea pig A 1 adenosine receptor have been isolated by polymerase chain reaction (PCR) and low-stringency hybridization screening of a guinea pig brain cDNA library. These three cDNAs, though differing in their 5′ untranslated regions, contain the same open reading frame encoding a 326 amino acid residue protein with seven hydrophobic α-helices long enough to form the transmembrane domains, suggesting that it belongs to the G protein-coupled receptor superfamily. This protein is highly homologous to the A 1 adenosine receptors previously cloned from other species. Pharmacological characterization of this receptor transiently expressed in mammalian cells demonstrates that, despite its high homology to A 1 adenosine receptors of other species, the guinea pig A 1 adenosine receptor displays a unique pharmacological profile: high affinity for the A 1-selective antagonist CPX, yet very low affinity for some A 1-selective agonists such as CCPA, CHA and R-PIA. Northern blotting for different guinea pig tissues and in situ hybridization for guinea pig brain sections reveal an abundant and broad distribution of mRNA of this A 1 subtype receptor in the brain.