The specific aims of our research are to define mechanisms of gastric acid secretion and gastrointestinal hormone release in humans; to develop and evaluate new methods of measuring gastric function under physiologic conditions in humans; to study pathophysiological defects in patients with peptic ulcer disease; to study the effect of vagotomy in patients with peptic ulcer disease and Zollinger-Ellison syndrome; to develop and study new methods of treating patinets with peptic ulcer; and to evaluate gastric function in patients with diabetes mellitus. To accomplish these goals, gastric acid secretion will be measured by aspiration and by in vivo intragastric titration, a method that allows measurement of acid secretion with food in the stomach. Vagal function will be evaluated by sham feeding normal subjects and patients with ulcer disease. We are also developing methods to measure bicarbonate secretion in humans. Our studies during the past 5 years have led to a number of interesting and we think important questions which we hope to anser during the next grant period. We will study the mechanism by which neural stimulation releases gastrin in man and will evaluate mechanisms controlling food-stimulated gastrin release. We will also determine whether prolonged gastric alkalinization is a stimulus for gastrin synthesis and release. We have shown that endogenous opiates play a physiological role in acid secretion and we plan to study the mechanisms whereby this occurs. Animal studies have suggested that salival contains an acid inhibitory substance. We will determine whether or not this substance exists and plays a physiological role in acid secretion in humans. Pathophysiological studies wll include an evaluation of the increased food-stimulated acid secretory rates and maximal secretory capacity which are characteristic of duodenal ulcer patients. Additional studies will be performed to determine the cause of reduced maximal secretory capacity and increased serum gastrin concentration after vagotomy. We hope to define the natural history of epidemic gastritis with hypochlorhydria. In normal subjects and diabetic patients we will study volume-pressure-gastric emptying relationships. We plan two controlled clinical trials evaluating the role of environmenal stress in the incidence of complications and recurrence of duodenal ulcer.

Project Start
1976-12-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
McArthur, K E; Richardson, C T; Barnett, C C et al. (1996) Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study. Am J Gastroenterol 91:1104-11
Fiorucci, S; McArthur, K E (1991) Prostaglandin E2 desensitizes cAMP-mediated pepsinogen secretion in chief cells. Am J Physiol 261:G858-65
Inman, L; Lee, S K; Shah, I A et al. (1990) Effect of truncal vagotomy on parietal cell mass and antral gastrin cell mass in dogs. Gastroenterology 99:1581-92
Fiorucci, S; McArthur, K E (1990) Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells. Am J Physiol 259:G760-6
McArthur, K E; Feldman, M (1989) Gastric acid secretion, gastrin release, and gastric emptying in humans as affected by liquid meal temperature. Am J Clin Nutr 49:51-4
Faust, T W; Lee, E; Redfern, J S et al. (1989) Effect of prostaglandin F3 alpha on gastric mucosal injury by ethanol in rats: comparison with prostaglandin F2 alpha. Prostaglandins 37:493-504
Redfern, J S (1988) Prostaglandin synthesis and catabolism in the gastric mucosa: studies in normal rabbits and rabbits immunized with prostaglandin E2. Prostaglandins 36:355-72
Brown-Cartwright, D; Smith, H J; Feldman, M (1988) Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Gastroenterology 95:49-51
Podolsky, I; Storms, P R; Richardson, C T et al. (1988) Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer. A five-year experience. Dig Dis Sci 33:1057-63
Heylings, J R; Redfern, J S; Feldman, M (1988) Inhibitory effect of isoprenaline on gastric acid secretion in the rat. The role of endogenous histamine. Aliment Pharmacol Ther 2:419-28

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