The pharmacological activity of some new fluorescent small molecule histamine H2 receptor (H2-R) ligands, derived from aminopotentidine and squaramide, in the GTPase assay.

We characterized the pharmacological activity of some new fluorescent and nonfluorescent ligands derived from aminopotentidine and squaramide with respect to the interaction with human (h) and guinea pig (gp) H2R species isoforms on Spodoptera frugiperda (Sf9) cell membranes expressing H2R-Gsalpha fusion proteins. The pharmacological studies were performed in a radioactivity-based GTPase assay. Non-linear curve ?tting was performed using the computer program Prism 4.0 (GraphPad-Prism). Interestingly is that the aminopotentidine ligands labeled with S0536 dye showed a higher activity than the squaramide ligands labeled with the same fluorophor. Moreover, for some cases, the bulky fluorescent groups can even substantially increase ligand affinity. The study of comparative antagonist activity of new H2R ligands derived from aminopotentidine and squaramide in the GTPase assay suggests that there is no common, lock' for all, keys' at the H2R.