Endogenous prostaglandins and microflora modulate DNA synthesis and neuroendocrine peptides in the rat gastrointestinal tract.
BACKGROUND
Previous studies suggest that E2 prostaglandins and the microflora may participate in the regulation of endocrine cells and of gastrointestinal cell kinetics. Our aim is to examine the actions of endogenous prostaglandins and of the microflora on gastrointestinal cell proliferation and tissue levels of neuroendocrine peptides.


METHODS
Germfree and ex-germfree rats were treated with subcutaneous placebo or 1.5 mg/kg indomethacin for 3 days. All rats were labeled with 3H-methyl-thymidine, and biopsy specimens from different parts of the gastrointestinal tract were processed for autoradiography. DNA synthesis was estimated by the labeling index, except in the oxyntic mucosa, where the total number of labeled cells present in 7.5 mm mucosa was used. The concentration of neuroendocrine peptides was determined by radioimmunoassay.


RESULTS
In the germfree rat, indomethacin reduced DNA synthesis in the fundus, duodenum, and proximal jejunum (P < 0.05) and the number of villous cells throughout the small intestine (P < 0.05). Exposure to microflora increased DNA synthesis in the proximal and distal jejunum, ileum, and colon (P < 0.05 versus germfree controls) and the number of crypt cells in the distal small intestine and colon (P < 0.05) and reduced the number of villous cells in the small intestine (P < 0.05) but did not affect tissue concentrations of neuroendocrine peptides. Indomethacin increased the concentration of somatostatin in the stomach, duodenum, and colon of germfree rats (P < 0.001), the concentration of calcitonin gene-related peptide (CGRP) and enteroglucagon in the proximal and distal jejunum and ileum (P < 0.001), and the concentration of glucagon in the colon (P < 0.05). The concentrations of somatostatin, CGRP, and glucagon were lower in indomethacin-treated ex-germfree rats than in indomethacin-treated germfree rats (P < 0.01).


CONCLUSIONS
Indomethacin selectively reduced DNA synthesis in the upper gastrointestinal tract of germfree rats, indicating a basal stimulatory role for endogenous prostaglandins on cell proliferation. Endogenous prostaglandins modulate synthesis or release of gastrointestinal neuroendocrine peptides. Somatostatin may mediate indomethacin-induced reduction of DNA synthesis. The microflora stimulates cell proliferation and influences tissue levels of neuroendocrine peptides in a manner opposite to that of indomethacin.
Uribe
A
A
Dept. of Medicine, Karolinska Institute, Danderyd Hospital, Danderyd/Stockholm, Sweden.
Alam
M
M
Midtvedt
T
T
Smedfors
B
B
Theodorsson
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D004064:Digestive System / Q000378:metabolism* / Q000382:microbiology*; D005768:Gastrointestinal Hormones / Q000502:physiology*; D005856:Germ-Free Life; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009490:Neurosecretory Systems / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005768:Gastrointestinal Hormones; D018377:Neurotransmitter Agents; D011453:Prostaglandins; D004247:DNA; D007213:Indomethacin