Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?

Physiological Reviews
John L Wallace

Abstract

Except in rare cases, the stomach can withstand exposure to highly concentrated hydrochloric acid, refluxed bile salts, alcohol, and foodstuffs with a wide range of temperatures and osmolarity. This is attributed to a number of physiological responses by the mucosal lining to potentially harmful luminal agents, and to an ability to rapidly repair damage when it does occur. Since the discovery in 1971 that prostaglandin synthesis could be blocked by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), there has been great interest in the contribution of prostaglandins to gastric mucosal defense. Prostaglandins modulate virtually every aspect of mucosal defense, and the importance of this contribution is evident by the increased susceptibility of the stomach to injury following ingestion of an NSAID. With chronic ingestion of these drugs, the development of ulcers in the stomach is a significant clinical concern. Research over the past two decades has helped to identify some of the key events triggered by NSAIDs that contribute to ulcer formation and/or impair ulcer healing. Recent research has also highlighted the fact that the protective functions of prostaglandins in the stomach can be carried out by other mediator...Continue Reading

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