Defects in prostaglandin synthesis and metabolism in ulcer disease.

Abstract

Ulcers occur because of an imbalance between mucosal protective resistance and damaging luminal factors, allowing the latter to predominate. The primary injurious elements are acid and peptic activity. Bile reflux, drugs, and gastroduodenal stasis may alter the luminal milieu and act together with acid-peptic activity to produce injury, weaken mucosal resistance, or both. Since prostaglandins modulate several key mucosal protective mechanisms, and since some exogenous prostaglandins and their derivatives accelerate peptic ulcer healing, it seems plausible that prostaglandin deficiency may contribute to the development of peptic ulcers. At the present time, however, evidence for this postulate is mostly indirect and can be summarized as follows: (1) Defects of mucosal protective mechanisms modulated by prostaglandins have been found in different forms of ulcer disease. Such defects include impaired duodenal bicarbonate secretion, deficient secretion or accelerated degradation of mucus, and reduced mucosal cell proliferation. (2) Drugs that inhibit cyclooxygenase, the key enzyme in tissue prostaglandin synthesis, have ulcerogenic activity. Presumably, in this situation, reduced prostaglandin production renders the mucosa more vulnerable to the action of acid and pepsin, or reduces the capability of the mucosa to repair itself. (3) Decreased mucosal prostaglandin synthesis or prostaglandin content has been found in patients with ulcer disease. Several studies have provided quantitative evidence of disturbed prostaglandin metabolism in some forms of ulcer disease. These studies are of high interest, but they need to be interpreted with caution given the present scientific debate regarding the physiological role of different prostanoids, as well as uncertainty as to the specific cellular source of prostaglandins in gastroduodenal mucosa.