Prostaglandins and ulcer healing.

Abstract

Exogenous prostaglandins (PG) applied in small gastroprotective doses fail to affect healing of gastro-duodenal ulcers but accelerate the healing when used in larger gastric inhibitory doses that appear to enhance COX-2 expression and PGE(2) generation in the ulcer area. COX-1 and COX-inhibitors delay ulcer healing, particularly when both COX isoforms are suppressed such e.g. by indomethacin. Dexamethasone, that decreases the expression of COX-2 and mucosal generation of PGE(2), delays ulcer healing that can be reversed by the addition of small dose of exogenous PGE(2). Proton pump inhibitors (PPI) such as omeprazole and PGE analogs, accelerate ulcer healing mainly due to potent inhibition of gastric acid secretion, but they also augment the COX-2 expression and enzyme activity in the ulcerated mucosa. Endogenous PG generated at ulcer margin appear to be involved in ulcer healing promoted by growth factors and gut hormones such as gastrin or CCK and melatonin acting, at least in part, through increase of induction of COX-2 and local release of PGE(2) in the ulcer area. The ulcer healing activity of growth factors (e.g. EGF, TGF alpha, HGF) and certain gut hormones (gastrin, CCK) as well as melatonin, can be attenuated by treatment with COX-1 or COX-2 inhibitors which suppress the release of PGE(2) but enhance the expression of COX-2. It is concluded that endogenous PG originating mainly from upregulated COX-2 at the ulcer margin play crucial role in ulcer healing by exogenous PG, PPI, growth factors, gut hormones and melatonin, while COX-1 and COX-2 inhibitors delay ulcer healing by suppressing PG generation, and increasing COX-2 expression in the ulcer area.

• Authors: S J Konturek, P C Konturek, T Brzozowski
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 56 Suppl 5 Pg. 5-31 (Sep 2005) ISSN: 1899-1505 [Electronic] Poland
• PMID: 16247187 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Ulcer Agents
• Cyclooxygenase Inhibitors
• Prostaglandins
• Cyclooxygenase 1
• Cyclooxygenase 2
• Dinoprostone

Topics

• Animals
• Anti-Ulcer Agents (administration & dosage, pharmacology)
• Cyclooxygenase 1 (drug effects, metabolism)
• Cyclooxygenase 2 (drug effects, metabolism)
• Cyclooxygenase Inhibitors (adverse effects)
• Dinoprostone (biosynthesis, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Humans
• Peptic Ulcer (drug therapy, physiopathology)
• Prostaglandins (administration & dosage, pharmacology)
• Rats