Evaluation of novel compounds interacting with H2-histamine receptors: effect on histamine-sensitive adenylate cyclase activity in guinea-pig gastric mucosa.
The activity of a number of compounds belonging to the novel class of N-imidazolylphenyl-N'-alkyl-formamidines on histamine-sensitive adenylate cyclase was evaluated. All substances inhibited histamine-dependent adenylate cyclase activation. The compounds which were investigated in a wider concentration range, i.e. DA 4360, DA 4577, and DA 4626, behaved as simple competitive antagonists, yielding apparent KB values comparable with those estimated in conventional H2-receptor assays. These results provide further evidence for the highly selective H2-receptor antagonism of these new molecules, and confirm the suitability of the histamine-stimulated adenylate cyclase assay in guinea-pig gastric cells as a functionally reduced system for the study of H2 antagonists.
Micheletti
R
R
Oliva
D
D
Belfiore
P
P
Giachetti
A
A
Nicosia
S
S
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001667:Binding, Competitive; D002927:Cimetidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005753:Gastric Mucosa / Q000201:enzymology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male
D000067956:Adenylyl Cyclase Inhibitors; D006635:Histamine H2 Antagonists; D007093:Imidazoles; C039796:mifentidine; D002927:Cimetidine; D006632:Histamine; C046831:DA 4360; C046830:DA 4626; C023990:tiotidine