Quantification of H2-agonism by clonidine and dimaprit in an adenylate cyclase assay

Abstract

In homogenates of guinea-pig ventricle clonidine and dimaprit both stimulate adenylate cyclase and exhibit ‘bell-shaped’E/[A] curves. The two properties (stimulatory and inhibitory) could be resolved using a theoretical model assuming a ‘down line’ auto-inhibitory mechanism. In the case of clonidine a further depressive property could be seen in the presence of high concentrations of the selective H₂-receptor antagonist tiotidine which is not explicable in terms of this model. The results suggest that clonidine has a direct agonistic effect on H₂-receptors in guinea-pig heart. However, like dimaprit, clonidine appears to be a partial agonist because its expression is confounded by a secondary inhibitory property(ies).