Is [³H]-tiotidine a specific ligand for the H₂-receptor?

The H₂-antagonist tiotidine inhibited the H₂-receptor-mediated, histamine-induced increase in cyclic AMP in dispersed mucosal cells from guinea pig stomach (K_i, 4 × 10^-8 M). The radiolabeled [³H]-tiotidine bound specifically and reversibly to the same cells with a half-maximal binding occurring at 5 × 10^-7M tiotidine. The dissociation of bound [³H]-tiotidine from gastric cells and the Scatchard analysis of the binding data suggest the existence of additional binding sites for tiotidine. Eight other antagonists which inhibited the H₂-receptor-mediated increase in cyclic AMP also inhibited [³H]-tiotidine binding. However, the potencies of these agents for binding did not agree with their effects on cyclic AMP. The selective H₂-agonists impromidine and dimaprit which increased cyclic AMP caused only partial inhibition of [³H]-tiotidine binding. These results demonstrate that [³H]-tiotidine has limited binding to the H₂-receptors and as such [³H]-tiotidine is not a suitable ligand for labelling the H₂-receptor on gastric mucosal cells.