Long term effects of H2-receptor antagonists (cimetidine and ranitidine) on the human gastric and duodenal mucosa.

Cytological effects of two H2-receptor antagonists on the gastric and duodenal mucosa were studied during therapy of active duodenal ulcer (D.U.) in man. After endoscopic diagnosis (day 0), subjects were treated with cimetidine or ranitidine and re-examined on day 30. Only subjects with healed D.U. on day 30 were retained in this study. Gastric, pyloric and duodenal endoscopic biopsies were taken and treated for further morphometrical analysis both by light and electron microscopy. The use of the immunoperoxidase technique allowed evaluation of G and D cell populations. Kinetic parameters in proliferative zones were measured after in vitro incubation of biopsies with 3H-thymidine. No differences could be seen between the two H2-receptor antagonists. Increase of tubulovesicles and decrease of canaliculi in parietal cells are closely related to the inhibitory effect of these drugs on acid secretion. However secretory capacities of parietal cells are preserved since the whole membrane (tubulovesicle + canaliculi surface) remained constant. The collapsed aspect of the tubulovesicles on day 30 and the presence of connections between the tubulovesicle membrane, with both vesicle and canaliculi membrane, could support the theory of osmotic membrane expansion during parietal cell acid secretion. H2-receptor antagonists have been shown to be trophic in duodenal mucosa: both villi and microvilli area are increased. Confirming these findings, the proliferative compartment in the intestinal crypts was shown to be enlarged. No variation of G cell number could be seen in the antral mucosa; clear intracytoplasmic granules were increased in D.U. on day 0 but were not further modified on day 30. Somatostatin labelling index decreased. These last findings associated with the lack of G cell variations, suggest the presence of a possible paracrine modulation in the gastric and duodenal mucosa.