Quantification of H2-agonism by clonidine and dimaprit in an adenylate cyclase assay.
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).
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D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D002927:Cimetidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D017259:Dimaprit; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013890:Thiourea / Q000494:pharmacology*
D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D000262:Adenylyl Cyclases; C023990:tiotidine; D013890:Thiourea; D003000:Clonidine; D017259:Dimaprit