Treatment with ghrelin accelerates the healing of acetic acid-induced gastric and duodenal ulcers in rats.
Recent studies have shown that ghrelin exhibits gastroprotective effects. The aim of present study was to examine the influence of ghrelin administration on the healing of chronic gastric and duodenal ulcers and to evaluate the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this process. In pituitary-intact or hypophysectomized rats, chronic gastric and duodenal ulcers were induced by acetic acid. After induction of ulcers, rats were treated intraperitoneally twice a day with saline, ghrelin (4, 8 or 16 nmol/kg/dose) or IGF-1 (20 nmol/kg/dose) for six or ten days. In animals with intact pituitary, treatment with ghrelin increased serum level of GH and IGF-1. These effects were accompanied by the increase in mucosal cell proliferation, mucosal blood flow and healing rate of gastric and duodenal ulcers. After hypophysectomy, the significant increase in serum level of endogenous ghrelin was observed, but the healing of gastric and duodenal ulcers was delayed. This effect was accompanied by a significant decrease in serum concentration of endogenous GH and IGF-1, and reduction in mucosal blood flow and DNA synthesis. In hypophysectomized rats, administration of exogenous ghrelin was without any effect on serum level of GH and IGF-1, healing rate of gastroduodenal ulcers or mucosal cell proliferation. In contrast to this effect, administration of IGF-1 increased mucosal cell proliferation, healing rate of gastroduodenal ulcers and mucosal blood flow in hypophysectomized rats.


CONCLUSIONS
Treatment with ghrelin accelerates healing of chronic gastroduodenal ulcers and this effect is mediated by the release of endogenous GH and IGF-1.
Department of Physiology, Jagiellonian University Medical College, ul. Grzegorzecka 16, Krakow, Poland.
P
P
Ceranowicz
Z
Z
Warzecha
A
A
Dembinski
R
R
Sendur
J
J
Cieszkowski
D
D
Ceranowicz
W W
WW
Pawlik
A
A
Kuwahara
I
I
Kato
P C
PC
Konturek
D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000188:drug therapy*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D054439:Ghrelin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy*
D000897:Anti-Ulcer Agents; D054439:Ghrelin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA; D019342:Acetic Acid