The ligand binding signatures of the rat AT1A, AT1B and the human AT1 receptors are essentially identical.

The objective of this study was to determine whether the three isoforms of recombinant Ang II receptors (rAT1A, rAT1B and hAT1), stably and individually expressed in CHO cells, could be pharmacologically distinguished by their ligand binding signatures. Competition studies were performed to characterize the inhibition of [125I]Ang II binding to each of the cell membrane preparations by an extensive series of peptide and nonpeptide Ang II analogs. Scatchard plot analyses revealed the following binding characteristics:rAT1A-Kd = 1.27 +/- 0.14 nM; rAT1B- Site 1:Kd = 0.56 +/- 0.11 nM, Site 2: Kd = 126 +/- 23 nM; and hAT1-Site 1:Kd = 1.06 +/- 0.16 nM, Site 2: Kd = 257 +/- 55 nM. The binding of [125I]Ang II in the three preparations was similarly sensitive to inhibition by GTP gamma S. The ligand binding signatures of the three receptor isoforms are essentially the same and are illustrated by the affinity and order of potency of the following ligands: L-158,809 > or = Sar1, Ile8Ang II > saralasin Ang II > or = Ang III > EXP581 > EXP3174 > losartan > or = EXP811 > GR117,289c > EXP6803 > DuP 532 > Ang I >> PD123177. In conclusion, the two rat AT1 receptor isoforms are pharmacologically indistinguishable from each other and from that of the human.