The turkey β-adrenoceptor and turkey β4C-adrenoceptor, unlike the turkey β3C-adrenoceptor, have two agonist conformations Of the 3 human β-adrenoceptors (AR), the β1 and β2-AR have been shown to exist in at least 2 active agonist conformations (Baker 2005a and b). There are three turkey β-AR – turkey β (Aurbach etal., 1975), 3C and 4C (Chen et al., 1994). This study looked for evidence of whether the 3 turkey β-ARs exist in different agonist conformations. CHO-K1 cells were transfected with either the original full length turkey β-AR, the turkey β3C-AR or β4C-AR. The full length turkey β-AR did not express so a construct with 59 amino acids deleted from the C-terminus was transfected (tβtrunc; Warne et al., 2008). Stable clonal cell lines were made by dilution cloning. 3H-cAMP accumulation was performed as previously described (Baker 2005b). Cyanopindolol (CYP) and CGP 12177 stimulated responses best described by a two-component curves for both the tβtrunc and tβ4C AR. The CYP and CGP 12177 responses in the tβ3C-AR were however best described by a single site sigmoidal concentration response curve. The inhibition of cimaterol by CGP 12177 for the tβ3C-AR (Fig C) can be expected by a competition at the same site. However, the pattern of inhibition of cimaterol by CGP 12177 at the tβtrunc-AR (Fig A) and tβ4C-AR (Fig B) can only be explained by the presence of at least two active conformations. Thus, the turkey βtrunc and tβ4C-AR appear to exist in two active agonist conformations. As yet there is no evidence of more that one active agonist conformation for the tβ3C-AR.
Table. Log EC50 values and % max isoprenaline responses for 3H-cAMP accumulation responses ![]()
Aurbach GD, Spiegel AM, Gardner JD. (1975) Adv Cyclic Nucleotide Res. 5:117-132.
|
||||||||||||||||||||||||||||||||||||||||||||||||||