Effect of a new potent H2-receptor antagonist 3[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-N2- sulfamoylpropionamidine (YM-11170) on gastric mucosal histamine-sensitive adenylate cyclase from guinea pig.
The effect of 3[[[2-[(diaminomethylene)amino]-4- thiazolyl]methyl]thio]-N2-sulfamoylpropionamidine (YM-11170), a new thiazole H2-receptor antagonist bearing propionamidine at the terminus of a side chain, on histamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] of gastric mucosa from the guinea pig was studied and compared with that of cimetidine. YM-11170 displaced the concentration-stimulation curve of histamine-sensitive adenylate cyclase to the right with a pA2 of 7.65 (Ki = 2.25 X 10(-8) M). Stimulation of gastric adenylate cyclase by 0.1 mM histamine was competitively inhibited by YM-11170 and cimetidine in a dose-dependent manner, with IC50 values of 5.9 X 10(-7) M and 1.4 X 10(-5) M respectively. Hippocampal histamine-sensitive adenylate cyclase in the presence of 0.1 mM histamine was also competitively inhibited by YM-11170 with an IC50 of 1.1 X 10(-7) M. YM-11170 did not affect Gpp(NH)p-, NaF-, PGE2-stimulated or basal activity of the gastric adenylate cyclase. These data, together with other results, indicate that YM-11170 is a highly selective and potent H2-receptor antagonist which competes with histamine at the receptor site on the histamine-sensitive adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D015738:Famotidine; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D006168:Guinea Pigs; D006624:Hippocampus / Q000201:enzymology; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D011458:Prostaglandins E; D013844:Thiazoles; D015738:Famotidine; D002927:Cimetidine; D006632:Histamine; D000262:Adenylyl Cyclases; D015232:Dinoprostone