Prostaglandin E2 influences the gastrointestinal endocrine cell system in the rat

Abstract

Previous studies suggest that prostaglandin E2 may interact with gastrointestinal endocrine cells. Our aim was to examine whether erogenous and endogenous prostaglandins - particularly prostaglandin E2 - influence the endocrine cell system in the rat gastrointestinal tract. Indomethacin was used to inhibit the synthesis of endogenous prostaglandins in order to gain information about a potential modulator role of the prostanoids on the endocrine cells. Sprague-Dawley rats were treated with oral prostaglandin E2 or a methyl- analogue for four weeks, or with subcutaneous indomethacin or indomethacin and prostaglandin E2 for eight weeks. The total volume of immunoreactive endocrine cells was evaluated quantitively using stereological methods and the tissue and plasma concentrations of neuroendocrine peptides were analysed with radioimmunoassay. The epithelial DNA synthesis was evaluated with the labelling index.

In the upper gastrointestinal tract, endogenous prostaglandins, particularly prostaglandin E2, induced an inhibitory tonus on the total volume of ECL and somatostatin cells and on the tissue concentration of somatostatin in the gastric fundus, as shown by the increased total volumes of immunoreactive cells and increased tissue concentrations of the peptide observed in the rats given indomethacin. In contrast. endogenous prostaglandins, particularly prostaglandin E2, induced a stimulatory tonus on the total volume of enterochromaffin cells in the antnim and on the total volumes of duodenal enterochromaffin cells and CCK and GIP-producing cells. The simultaneous administration of prostaglandin E2 reversed - partially or completely - the changes elicited by indomethacin. Exogenous E2 prostaglandins influenced the ECL cells and the somatostatin cell population in the fundic mucosa and increased the plasma levels of somatostatin. Exogenous E2 prostaglandins increased the total volume of serotonin and gastiin/CCK-immunoreactive cells in the duodenum.

In the lower gastrointestinal tract, endogenous prostaglandins, particularly prostaglandin E2, induced an inhibitory tonus on the synthesis and/or release of tissue somatostatin in the ileum. DNA synthesis was increased in the small intestinal crypts in animals depleted of prostaglandins, which was associated with increased tissue concentrations of neurokinin A, neurotensin and glucagon. Exogenous E2 prostaglandins influenced the total volume of glucagon/glicentin-immunoreactive cells in the jejunum. and the tissue concentration of somatostatin and glucagon. E2 prostaglandins influenced the total volume of glucagon/glicentin- and somatostatin-immunoreactive cells in the colonic mucosa.

In conclusion, the modulation and/or influence of endogenous and erogenous prostaglandins, particularly prostaglandin E2, on the ECL, enterochromaffin, CCK, glucagon and somatostatin cell in the gastrointestinal tract - including synthesis and/or release of neuroendocrine peptides - suggest that endogenous and erogenous prostaglandins may indirectly participate in important biological functions that are modified by neuroendocrine peptides. Taken together with other observations, our findings indicate that the regulation of the the gastrointestinal endocrine cell system is multifactorial and that intraluminal factors, particularly the colonic microflora, may mask and/or modify the actions of endogenous prostaglandins on endocrine cells.