Action of somatostatin analogue (SMS 201-995) on the growth-promoting effect resulting from sustained achlorhydria in rat gastric mucosa, with special reference to endocrine cell behaviour.

Abstract

We investigated whether a new long-acting somatostatin analogue (SMS 201-995) could antagonize the trophic effect induced by hypergastrinaemia, resulting from chronic omeprazole treatment, on the rat gastric mucosa and particularly on endocrine cell growth. SMS was administered concomitantly with omeprazole for 70 days. Gastric morphometric and cell proliferative parameters, gastric acid secretion and plasma gastrin levels were examined. New findings with omeprazole pointed out: (i) a trophic effect on the antral mucosa and (ii) that the increase observed in gastrin cell number was not due to stimulation of gastrin cell production by omeprazole but more likely to a prolongation of the gastrin cells' life span. As compared to omeprazole alone, simultaneous SMS administration significantly decreased the parietal cell (P less than 0.05) and gastrin cell (P less than 0.01) labelling indices, mucosal height of total glandular stomach (P less than 0.05) and antral mucosal height (P less than 0.05). It tended to lower fundic mucosal height and fundic argyrophil cell density (P less than 0.2 and P less than 0.1, respectively). SMS, in our conditions, did not accentuate the inhibitory effect of omeprazole on gastric acid secretion nor reduce high plasma gastrin levels. We conclude that SMS modestly counteracts the growth-promoting effect observed in rat gastric mucosa after prolonged omeprazole treatment.