Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: role of gastrin and epidermal growth factor.
Growth hormone-releasing factor (GRF) was reported to possess the growth-promoting action on the gastroduodenal mucosa that can be augmented by removal of endogenous somatostatin. Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats. GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA. GRF also significantly increased serum gastrin levels and the tissue contents of epidermal growth factor (EGF) in salivary glands, duodenum and pancreas, suggesting that both gastrin and EGF could contribute to mucosal trophic and ulcer healing effects of GRF. Somatostatin (100 micrograms/kg/day for 7 days) abolished almost completely the ulcer healing and mucosal growth-promoting effects of GRF and this was accompanied by the reduction in serum gastrin level and the tissue contents of EGF suggesting that the suppression of gastrin and EGF release could contribute to the observed effects of somatostatin. We conclude that GRF has both the ulcer healing and the mucosal trophic actions which can be antagonized by somatostatin and that gastrin and EGF may be implicated in these actions.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Brzozowski
T
T
Dembinski
A
A
Warzecha
Z
Z
Konturek
P K
PK
Yanaihara
N
N
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D004815:Epidermal Growth Factor / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects; D005755:Gastrins / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D013004:Somatostatin / Q000502:physiology* / Q000627:therapeutic use; D014945:Wound Healing
D000085:Acetates; D005755:Gastrins; D013004:Somatostatin; D004815:Epidermal Growth Factor; D013007:Growth Hormone-Releasing Hormone; D019342:Acetic Acid