Prostaglandins and the dog stomach: effects of misoprostol on the proportion of mucosa to muscle and on the proportion of different epithelial cell types.

Dogs were given an oral dose of 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol for 11 weeks. The relative areas of the main components of the fundus and antrum per unit area of serosa were quantified. While the volume occupied by the muscle layers did not change, there was an increase in mucosal volume in both sites. The relative volume fraction of the main mucosal cell types was then determined by a point counting technique. Misoprostol very highly significantly increased the fraction of mucosal volume occupied by surface mucus cells, and also significantly decreased the volume fraction of the parietal cells.

The effects of the prostaglandin analogue, misoprostol, on cell proliferation and cell migration in the canine stomach.

Increased mucosal mass is associated with prostaglandin administration, raising the question as to whether this is the consequence of increased cell production or decreased cell loss. 3H-thymidine was injected into 30 test dogs given 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol, orally for 11 weeks, and into 30 dogs which had been given the vehicle alone. Six test and 6 control dogs were killed 1 h after thymidine labelling, and the remainder were killed subsequently at timed intervals to determine cell migration rates and transit times. Misoprostol significantly increased the stomach weight, but nonetheless did not significantly increase the labelling index, nevertheless, the number of labelled cells per gland was significantly increased, which was a consequence of the increased gland length. When the data was expressed as a gland cell production rate significant increases were thus observed. The migration rate of cells toward the gastric lumen increased one and a half times in the misoprostol-treated group; however, as the gland length also significantly increased, there was no significant difference in the transit time. It must be concluded that the hyperplasia associated with exogenous prostaglandins is the consequence of increased cell production, not decreased cell loss, and that previous reports to the contrary are the result of failure to allow for concomitant changes in the denominator of proliferative indices.

Effects of misoprostol on cell migration and transit in the dog stomach.

Prostaglandins of the E series increase stomach mucosal mass by inducing hyperplasia, which could be the result either of increased cell production or of decreased cell loss. This report describes an investigation of the effect of the prostaglandin E1 analogue, misoprostol, on cell migration and transit. 3H-thymidine was used to label those cells synthesizing deoxyribonucleic acid in dogs that had been given an oral dose of 300 micrograms/kg per day misoprostol for 11 weeks. The animals were killed at timed intervals, and tissue from the gastric fundus was prepared for autoradiography. The distribution of labeled cells at various times after labeling was used to follow the movement of the wave of label and to calculate median cell migration rates and transit times. The migration rate of cells toward the gastric lumen was significantly increased from 1.4 +/- 0.3 to 3.6 +/- 0.6 cell positions per day in the misoprostol-treated group (p less than 0.001); however, the gland length (from the most basal mucous neck cell to the luminal surface) was also increased (from 52.1 +/- 1.1 to 74.0 +/- 1.6; p less than 0.001), thus there was no significant difference in the (transit) time taken for cells to reach the top of the gland (control, 17.5 +/- 9.8 days; test, 12.2 +/- 7.1 days).

Prostaglandins and the gastric epithelium: effects of misoprostol on gastric epithelial cell proliferation in the dog.

The effects of the methyl ester analogue of prostaglandin E1, misoprostol, on gastric epithelial cell proliferation were investigated in six dogs given 300 micrograms/kg/day of misoprostol orally for 11 weeks and in six control dogs given placebo for 11 weeks. Misoprostol treatment resulted in a 36% increase in stomach weight (p less than 0.01) and a 30% increase in the length (measured as the cell column count from the base/neck junction to the surface) of the fundic gastric glands (p less than 0.01). This mucosal hyperplasia was predominantly caused by enlargement of the foveolar region of the gland, with little change occurring in the neck or in the isthmus. The hyperplasia was the result of an increased number of mitotic (p less than 0.01) and DNA synthesising cells (p less than 0.05) in each gastric gland, which resulted in a significant increase in the gland cell production rate, from 22.5 to 42.6 cells per gland per day (p less than 0.05).