Mechanisms of gastroprotection.
Gastric mucosa is constantly exposed to various irritants, but it usually maintains its integrity owing to several lines of defense, including mucus-alkaline secretion, mucosal hydrophobicity, rich mucosal blood flow, stabilization of tissue lysosomes, maintenance of mucosal sulfhydryls, and rapid proliferation and renewal of mucosal cells. Prostaglandins (PG) inhibit experimental gastric mucosal damage and ulcerations induced by a wide variety of agents, hence PG have been proposed to contribute to the overall protective process by activation of various mucosal defence lines--particularly by prevention of vasocongestion, ischemia, and deep hemorrhagic necrosis. The relation between tissue PG generation and mucosal protection does not appear to be closely related, and probably only minute amounts of PG are required to maintain mucosal integrity. In contrast to PG, other products of arachidonate metabolism, such as TxA2, LTC4 or LTD4, and the related lipid, platelet-activating factor, appear to mediate mucosal damage mainly by the disturbance in mucosal microcirculation and tissue ischemia. Gastroprotection can be achieved by stimulation of mucosal biosynthesis of protective PG or by the inhibition of the release or action of the proulcerogenic arachidonate metabolites. Certain natural substances, such as sulfhydryls, epidermal growth factor, or polyamines, protect the mucosa via a PG-independent mechanism, probably by enhancing the tissue repair processes.(ABSTRACT TRUNCATED AT 250 WORDS)
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Cracow, Poland.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001241:Aspirin / Q000633:toxicity; D015777:Eicosanoids / Q000502:physiology; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009093:Mucus / Q000378:metabolism; D010437:Peptic Ulcer / Q000188:drug therapy / Q000517:prevention & control; D011453:Prostaglandins / Q000502:physiology
D000897:Anti-Ulcer Agents; D015777:Eicosanoids; D011453:Prostaglandins; D000431:Ethanol; D001241:Aspirin