Role of prostaglandins in gastroprotection and gastric adaptation

• Autorzy: Brzozowski T. , Konturek P.C. , Konturek S.J. , Brzozowska I. , Pawlik T.
• Języki publikacji: EN

Abstrakty

EN

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenaxe (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hiperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE2 or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhamcement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE2 generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

Słowa kluczowe

EN

gastric blood flow; calcitonin gene releasing peptide; gastroprotection; ulcer healing; nitric oxide; pretreatment; gastric mucosa; gastric adaptation; ischaemic preconditioning; prostaglandin; cyclooxygenase

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2005
• Tom: 56
• Numer: 5
• Strony: 33-55
• Opis fizyczny: p.33-55,fig.,ref.

Twórcy

autor

Brzozowski T.

• Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Krakow, Poland

autor

Konturek P.C.

autor

Konturek S.J.

autor

Brzozowska I.

autor

Pawlik T.