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069P Queen Elizabeth II Conference Centre London
BPS Winter Meeting 2009

 

The 3H-CGP 12177 whole cell binding characteristics of the three turkey β-adrenoceptors

Jillian Baker. University of Nottingham, Nottingham, United Kingdom.

 

There are three turkey β-adrenoceptors (AR) – turkey β (Aurbach etal., 1975), 3C and 4C (Chen et al., 1994). Although the turkey β-AR has similar sequence to the human β1-AR (Warne et al.,2008) it is not known whether the pharmacological binding characteristics are similar. The turkey β4C receptor has been reported to be unlike the turkey β-AR (Chen et al.,1994). No data have been published for the turkey β3C receptor. This study examined the binding characteristics of the 3 turkey β-ARs and compared them to the 3 human β-ARs.

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 C-terminally truncated version was transfected (tβtrunc). Stable clonal cell lines were selected by dilution cloning. 3H-CGP 12177 whole cell binding was performed as previously described (Baker 2005).

When the log KD values for a wide range of ligands are plotted against the log KD values from the human β-ARs (data from Baker 2005 and abstract at this meeting) it can be seen that the tβ3C receptor most closely resembles the human β2-AR Figure A). There are some marked differences between the tβtrunc receptor and the human β1-AR (Figure B) and the tβ4C receptor is unlike any of the human B-AR or other turkey β-ARs.

 

tβtruncntβ3Cntβ4Cn
Betaxolol -6.90±0.04 6 -6.29±0.08 8 -6.24±0.06 7
Bisoprolol -6.70±0.03 6 -5.58±0.08 6 -6.26±0.08 7
CGP20712A -7.53±0.04 8 -5.40±0.11 9 -6.05±0.07 12
Cyanopindolol -10.89±0.06 6 -11.37±0.07 6 -10.81±0.09 6
Fenoterol -6.36±0.03 6 -6.69±0.07 10 -6.22±0.10 10
Formoterol -7.33±0.06 6 -7.96±0.07 7 -7.70±0.07 7
ICI118551 -7.20±0.03 5 -8.93±0.06 9 -7.37±0.03 9
Salmeterol -5.92±0.04 8 -8.50±0.07 8 -7.09±0.04 8

 

Table. Log KD values from 3H-CGP12177 whole cell binding.

 

 

JGB is a Wellcome Trust Clinician Scientist Fellow.
Aurbach GD, Spiegel AM, Gardner JD. (1975) Adv Cyclic Nucleotide Res. 5:117-132.
Baker JG (2005). Brit J Pharmacol 144: 317-222.
Chen XH, Harden TK, Nicholas RA. (1994) J Biol Chem. 269: 24810-9.
Warne T et al., (2008) Nature 454: 486-491.