Action of histamine and of some H2-antagonists on gastric secretion 'in vitro'

The effect of histamine and of some H2-antagonists on isolated gastric mucosal preparation from immature (14-18 days) rats, was investigated. Basal secretion varied, in our experimental conditions, between 1.06 and 3.54 mumol cm-2 h-1, reaching higher values (approximately 4.6 mumol cm-2 h-1) only in a small percentage of animals (10%). Histamine exerted a concentration-dependent stimulation of acid secretion in concentrations varying between 2 X 10(-6) and 1.6 X 10(-4) M. The response to histamine was competitively antagonized by ranitidine (pA2 value = 6.78) and by 4(5)-(4- isopropylaminomethyleniminophenyl ) imidazole (compound marked DA 4577) (pA2 value = 7.37). Oxmetidine acted as a competitive antagonist only for concentrations as low as 10(-8) M; higher concentrations (10(-7) and 10(-6) M) determined a non-competitive inhibition. Ranitidine and compound marked DA 4577 did not affect basal secretion up to concentrations of 3 X 10(-4) M. On the contrary oxmetidine exerted a concentration-dependent inhibition starting from 10(-5) M. Since in our experimental conditions the role of calcium ions in the regulation of basal secretion could not be established, the mechanism of action of oxmetidine was not completely clarified, even if an interference in the utilization of calcium ions may be suggested. In any case it is deemed of interest that this H2-antagonist was the only compound capable of inducing a reversible complete inhibition of basal acid secretion (only KSCN, in very high concentrations, had a similar behaviour).