科研之友
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摘要
Background: There are three turkey beta-adrenoceptors: the original turkey beta-adrenoceptor from erythrocytes (t beta trunc, for which the X-ray crystal structure has recently been determined), t beta 3C and t beta 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.
Methodology/Principal Findings: Stable cell lines were constructed with each of the turkey beta-adrenoceptors and (3)H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey beta-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey beta-adrenoceptors to human beta-adrenoceptors is between the turkey beta 3C-receptor and the human beta 2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the t beta trunc and t beta 4C and the human beta-adrenoceptors (e. g. with CGP20712A and ICI118551). The tbtrunc and t beta 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 beta 1-adrenoceptor and human beta 3-adrenoceptors. The t beta b3C-receptor, similar to the human beta 2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.
Conclusions/Significance: There are several similarities, but also several important differences, between the recently crystallised turkey beta-adrenoceptor and the human beta-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 beta-adrenoceptor conformation.
- 出版日期2010-11-30
