Dictyostelium cells exhibit four types of kinetically distinct surface cAMP binding sites, the A(H), A(L), B(S), and B(SS) sites, which are down-regulated during persistent stimulation with cAMP. Although most cAMP-induced responses are subject to desensitization during constant stimulation, some responses, notably the induction of post-aggregative gene expression, require persistent cAMP stimulation. The kinetics and specificity of residual cAMP-binding activity in cells treated for 4 h with micromolar cAMP were investigated. It was found that around 4000 rapidly dissociating binding sites per cell with an affinity of about 300 nM are retained after down-regulation. The nucleotide specificity of the remaining sites was very similar, but no...