Effects of oestrogens on carbonic anhydrase activity in human and canine gastric mucosa. The role of carbonic anhydrase inhibitors in the treatment of peptic ulcer - abstract

ABSTRACT

Carbonic anhydrase which is present in abundance in the mammalian gastric mucosa is concerned with the production of hydrochloric acid. The aim of the present study was to determine whether oestrogens had any effects on the activity of this enzyme in the gastric mucosa of man and dogs. Biopsies were taken from the body of the stomach of 20 male duodenal ulcer patients, 10 of whom had a pre-operative course of diethylstilboestrol. Ten male dogs were used in the animal experiments. Immediately after a biopsy was taken from the anerior wall of the stomach, midway between the cardiac end and the pylorus, 40 mg of equine conjugated oestrogens were injected intravenously in the dogs. Thirty minutes later a second specimen was collected from a site adjacent to the first one. The homogenate obtained from the mucosal layer of each specimen was used for the estimation of its carbonic anhydrase activity by the colorimetric method of Philpot and Philpot. Reaction times were also noted for various dilutions of pure hyophilized carbonic anhydrase. On the basis of a two-tailed test using a 't' distribution it was found that there is a significant difference in the results before and after injection of equine conjugated oestrogens and between the stilboestrol treated patients and the controls. A mean inhibition of 43.5 percent was achieved in man and 21.2 percent in dogs. One patient who was 14 weeks pregnant had an inhibition of 63.4 percent compared with the controls. Truelove and other workers were convinced that ulcer patients experienced symtomatic relief when put on a course of stilboestrol. Similar results were reported in dogs. On the basis of the present work the oestrogens seem to be carbonic anhydrase inhibitors and hence can account for the regular occurrence of hypochlohydria during pregnancy and the lower incidence of peptic ulcer in women of the child-bearing age. Although acetazalamide has been found to reduce the severity of ulcer symptoms, this beneficial action was overshadowed by a concomitant production of persistent acidosis and tingling and numbness in the fingers. The use of carbonic anhydrase inhibitors for the treatment of peptic ulcer merits further investigations. An ideal drug would be a non-feminizing steroid with good peptic ulcer healing powers (AU)