[Effect of H2 histamine receptor blocking agents on the isolated lower esophageal sphincter (LES) of the rat].

A series of histamine H2-receptor antagonists were tested for their activity on the isolated lower esophageal sphincter (LES) of the rat. Burimamide, methiamide and cimetidine were found to be virtually inactive since they caused very weak contractions only with extremely high concentrations (up to 300 microgram/ml). Ranitidine exerted a contraction at each concentration tested (from 1 to 100 microgram/ml). Oxmetidine, the newest member of the family, caused a modest contraction in low concentrations (0.3 to 3 microgram/ml) but a remarkable relaxation in high concentrations (10 to 300 microgram/ml). A series of observations suggested that H2 receptors do not occur in the rat LES: a) the lack of interference on histamine-induced contractions by the H2-blockers; b) the effect of histamine was mimiced by 2-aminoethylthiazole (a selective H1-receptor agonist) and inhibited by chlorpheniramine (a H1-receptor antagonist); c) dimaprit (a selective H2-receptor agonist) failed to modify the LES tension even at the maximum doses tested. All of these observations are consistent with the idea that the effects of the H2-receptor antagonists showed in the present investigation are independent of H2-receptor blockade. The contracting effect of ranitidine which was inhibited by tetrodotoxin and abolished by atropine is probably connected with a stimulating of the cholinergic system so far never described in the literature. The relaxant effect of oxmetidine is apparently a myolitic effect independent of stimulation of specific receptors.