A full pharmacological analysis of the three turkey ?-adrenoceptors and comparison with the human ?-adrenoceptors.

ABSTRACT: There are three turkey ?-adrenoceptors: the original turkey ?-adrenoceptor from erythrocytes (t?trunc, for which the X-ray crystal structure has recently been determined), t?3C and t?4C-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.Stable cell lines were constructed with each of the turkey ?-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey ?-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey ?-adrenoceptors to human ?-adrenoceptors is between the turkey ?3C-receptor and the human ?2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the t?trunc and t?4C and the human ?-adrenoceptors (e.g. with CGP20712A and ICI118551). The t?trunc and t?4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat ?1-adrenoceptor and human ?3-adrenoceptors. The t?3C-receptor, similar to the human ?2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.There are several similarities, but also several important differences, between the recently crystallised turkey ?-adrenoceptor and the human ?-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 ?-adrenoceptor conformation.

SUBMITTER: Baker JG 

PROVIDER: S-EPMC2994877 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature