Can equal pA2 values be compatible with receptor differences?

Situations exist in which pA2 analysis leads to conclusions about receptor differentiation that conflict with those drawn from other convincing lines of evidence. Robert Raffa and colleagues address this issue in its broadest context, particularly in relationship to the concept of accessory binding sites, using the controversy of delta-opioid receptor-mediated antinociception as an example. When the possibility of accessory binding sites is considered, it becomes clear that the finding of equal pA2 values does not necessarily mean action at the same receptor, and that the finding of unequal pA2 values does not necessarily confirm action at different receptors.