Mechanism by which indomethacin delays gastric ulcer healing in the rat: inhibited contraction of the ulcer base.
Repeated administration of indomethacin delays the healing of acetic acid-induced gastric ulcers in rats, but the underlying mechanism remains unclear. We examined the effect of indomethacin on the contraction of the connective tissue isolated from the base of 1-week-old ulcers. The tissue samples, suspended in an organ bath, were contracted by serotonin, bradykinin and carbachol and also slightly contracted by prostaglandin (PG) F1 alpha. The effect of serotonin was the most potent. However, 6-keto-PGF1 alpha, PGE2 and histamine had little or no contraction inducing effect. The contractile response to serotonin of the tissue in the indomethacin-treated group was significantly less than that in the control group (without indomethacin treatment). After a 2-week treatment with indomethacin, a histological study of the ulcers showed that the length of rupturing of the muscularis mucosa was significantly greater than that observed in the control group. However, indomethacin had no effect on the length of the regenerated mucosa and the thickness of the ulcer base. We conclude that the connective tissue at the ulcer base has the ability to contract and that the prevention of the contraction of the tissue by indomethacin might be involved in the mechanism underlying delayed ulcer healing.
Ogihara
Y
Y
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okabe
S
S
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D003238:Connective Tissue / Q000187:drug effects; D005753:Gastric Mucosa / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000085:Acetates; D012701:Serotonin; D019342:Acetic Acid; D007213:Indomethacin