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 δ-opioid receptor-mediated antinociception as an example. When the possibility of accessory binding sites is considered, it becomes dear 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.