Effect of oral prostaglandin E2 on DNA turnover in gastric and intestinal epithelia of the rat.
The mucosal incorporation and clearance of a DNA precursor was examined in the rat stomach and intestine following oral treatment with natural prostaglandin E2 (PGE2) or 15(R) 15 methyl prostaglandin E2 (Me PGE2). Control groups received vehicle or pentagastrin. After five days of treatment animals were labelled with methyl-3H-thymidine. Groups of rats were killed at 0.75, 24, 72, 96 and 120 h after labelling. Treatments continued until killed. Mucosal scrapings were analysed for radioactivity and DNA. Morphometric measurements were performed and plasma levels of gastrin and somatostatin determined. PGE2 and its stable analogue produced hyperplasia within one week of treatment, in particular of the gastric antrum and changed the incorporation and clearance of radioactive thymidine from gastric and intestinal epithelia. The most consistent finding was a delayed elimination of thymidine from the mucosa, indicating a slowing of the DNA turnover. The DNA synthesis was differently affected along the gastrointestinal tract, being unchanged or reduced in the stomach and moderately increased in the intestine. Prostaglandin treatment was associated with a three- to ten-fold increase of the gastric acid contents and with elevated plasma levels of gastrin and somatostatin. It is concluded that E2 prostaglandins produce hyperplasia of gastric and intestinal epithelia in the rat by prolonging the cell survival time rather than by increasing new cell production. Hypergastrinemia is not a likely mediator of trophic actions of E2 prostaglandins, which develop despite elevated plasma levels of somatostatin.
D000284:Administration, Oral; D000818:Animals; D001101:Arbaprostil / Q000008:administration & dosage / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D015232:Dinoprostone; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006728:Hormones / Q000097:blood; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D006728:Hormones; D011458:Prostaglandins E; D004247:DNA; D015232:Dinoprostone; D001101:Arbaprostil; D013936:Thymidine