title: A full pharmacological analysis of the three turkey β-adrenoceptors and comparison with the human β-adrenoceptors.
abstract: BACKGROUND
  There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.
  
  
  RESULTS
  Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.
  
  
  CONCLUSIONS
  There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation.
authors.affiliation: Institute of Cell Signalling, University of Nottingham, Nottingham, United Kingdom. jillian.baker@nottingham.ac.uk
authors.forename: Jillian G
authors.initials: JG
authors.lastname: Baker
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014316:Tritium; D014421:Turkey
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D020033:Protein Isoforms; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D011433:Propranolol; D000242:Cyclic AMP; C033394:CGP 12177