Summary
Metabolites of arachidonic acid have a broad range of physiological functions in the gastrointestinal tract, and seem to be involved in certain disturbances of gastrointestinal integrity and function. Prostaglandins inhibit gastric acid secretion, apparently via an adenylate cyclaselinked receptor, and also stimulate bicarbonate and mucus production by alternative mechanisms. These are all beneficial in treating gastroduodenal ulceration. Moreover, clinical studies have revealed deficient prostaglandin synthesis in the gastric and duodenal mucosa of patients with gastrointestinal ulcers, which suggests that endogenous prostaglandins have a protective role in the gastrointestinal tract. In animal studies, prostaglandin analogues have been shown to protect the gastric mucosa from damage induced by various potent irritants, and this protection seems to involve the deeper layers of the mucosa as well as the epithelium. Indeed, misoprostol and other prostaglandin analogues have proved therapeutically effective in treating gastroduodenal ulceration.
Prostaglandins also influence intestinal motility and fluid movement. Prostaglandin E derivatives generally relax circular smooth muscle, contract longitudinal smooth muscle and increase fluid secretion into the intestinal lumen. As a result of these effects, prostaglandins may cause diarrhoea. There is also evidence that prostaglandin synthesis is increased in patients with diarrhoea.
Finally, it has been reported that tissue concentrations of prostaglandins are increased in patients with ulcerative colitis, but it is unclear if this is a primary cause, or secondary event. Significantly greater conversion of arachidonic acid to its metabolites was recorded in the mucosa of patients with inflammatory bowel disease compared with the mucosa of healthy subjects. This included a substantial increase in the concentration of leukotriene B4. Moreover, the drugs sulphasalazine and 5-amino-salicylic acid, which are used for the treatment of ulcerative colitis, markedly decreased the synthesis of leukotriene B4 and other products of arachidonic acid metabolism.
Thus, prostaglandins, in particular, have important effects on gastrointestinal function. They may have a beneficial effect in the treatment of gastric or duodenal ulcers. However, they can cause intestinal secretion and diarrhoea, and may play a pathogenetic role in ulcerative colitis.
Similar content being viewed by others
References
Basso N, Materia A, Forlini A, Jaffe BM. Prostaglandin generation in the gastric mucosa of rats with stress ulcer. Surgery 94: 104–108, 1983
Isenberg JI, Hogan DL, Selling JA, Koss MA. Duodenal bicarbonate secretion in humans: role of prostaglandins. Digestive Diseases and Sciences 31 (Suppl.): 130S, 1986
Lacy ER. Prostaglandins and histological changes in the gastric mucosa. Digestive Diseases and Sciences 30 (Suppl.): 83S–94S, 1985
Lam SK, Lau WY, Choi TK, Lai CL, Lok ASF, et al. Prostaglandin E1 (misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal ulcer healing. Digestive Diseases and Sciences 31 (Suppl.): 68S–74S, 1986
Lanza FL. A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects. Digestive Diseases and Sciences 31 (Suppl.): 131S–136S, 1986
Lichtenberger LM, Richards JE, Hills BA. Effect of 16,16-dimethyl prostaglandin E2 on the surface hydrophobicity of aspirin-treated canine gastric mucosa. Gastroenterology 88: 308–314, 1985
Mielants H, Verbruggen VG, Schelstraete K. Comparison of serum salicylate levels and gastro-intestinal blood loss between salsalate (Disalcid) and other forms of salicylate. Scandinavian Journal of Rheumatology 10: 169–173, 1981
Muller P, Fischer N, Kather H, Simon B. Prevention of aspirin-induced drop in gastric potential difference with 16,16-dimethyl prostaglandin E2. Lancet 1: 333–334, 1981
Nicholson PA. A multicenter international controlled comparison of two dosage regimens of misoprostol and cimetidine in the treatment of duodenal ulcer in outpatients. Digestive Diseases and Sciences 30 (Suppl.): 171S–177S, 1985
Rachmilewitz D. Role of endogenous prostanoids in pathogenesis of peptic ulcer. Postgraduate Medicine (Special Report): 79–83, 1985
Robert A. Cytoprotection by prostaglandins. Gastroenterology 77: 761–767, 1979
Sellers LA, Carroll NJH, Allen A. Misoprostol-induced increases in adherent gastric mucus thickness and luminal mucus output. Digestive Diseases and Sciences 31 (Suppl.): 91S–95S, 1986
Sharon P, Stenson WF. Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 86 (3): 453–460, 1984
Sharon P, Cohen F, Zifroni A, Karmeli F, Ligumsky M, et al. Prostanoid synthesis in cultured gastric and duodenal mucosa: possible role in the pathogenesis of duodenal ulcer. Scandinavian Journal of Gastroenterology 18(8): 1045–1049, 1983
Shield MJ. Interim results of a multicenter international comparison of misoprostol and cimetidine in the treatment of out-patients with benign gastric ulcers. Digestive Diseases and Sciences 30 (Suppl.): 178–184, 1985
Whittle BJR, Steel G. Evaluation of the protection of rat gastric mucosa by prostaglandin analogue using cellular enzyme marker and histologic techniques. Gastroenterology 88: 315–327, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Isselbacher, K.J. The Role of Arachidonic Acid Metabolites in Gastrointestinal Homeostasis. Drugs 33 (Suppl 1), 38–46 (1987). https://doi.org/10.2165/00003495-198700331-00007
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198700331-00007