Role of endogenous gastrin in gastroprotection.
Gastrin has a potent influence on gastric acid secretion and mucosal growth but its role in mucosal integrity has been little studied. This study investigated in rats whether gastrin protects the gastric mucosa against the damage by 100% ethanol and what are the possible mechanisms of this protection. Exogenous gastrin-17 (0.6-5.0 pmol/kg) injected subcutaneously (s.c.) reduced dose dependently ethanol-induced mucosal damage and the dose decreasing the ethanol lesions by 50% was about 1.8 pmol/kg. The protection afforded by gastrin-17 was accompanied by a dose-dependent increase in gastric blood flow and these effects were almost completely abolished by the pretreatment with specific CCKB (L-365,260) but not CCKA receptor antagonist (loxiglumide). Endogenous gastrin released by intragastric (i.g.) peptone meal or s.c. injection of gastrin-releasing peptide prevented the formation of acute ethanol-induced lesions and these effects were also abolished by the pretreatment with L-365,260 but not by loxiglumide. The inhibition of nitric oxide (NO) synthase, by NG-nitro-L-arginine methyl ester almost completely eliminated both the protective and hyperemic effects of gastrin-17 and the addition of L-arginine (but not D-arginine) to NG-nitro-L-arginine-methyl ester restored, in part, these effects of gastrin-17. Deactivation of sensory nerves with capsaicin did not influence the protective or hyperemic effects of gastrin-17. We conclude that both exogenous and endogenous gastrin exert its protective activity against ethanol damage of gastric mucosa and this effect is mediated through the interaction with specific CCKB receptors and arginine-NO pathway, but does not involve sensory nerves.
Konturek
S J
SJ
Institute of Physiology, Jagiellonian University School of Medicine, Kraków, Poland.
Brzozowski
T
T
Bielanski
W
W
Schally
A V
AV
D000818:Animals; D001241:Aspirin / Q000633:toxicity; D002211:Capsaicin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010455:Peptides / Q000627:therapeutic use; D010461:Peptones / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*
D005755:Gastrins; D010455:Peptides; D010461:Peptones; D009569:Nitric Oxide; D000431:Ethanol; C013550:gastrin 17; D019886:Gastrin-Releasing Peptide; D015232:Dinoprostone; D001241:Aspirin; D002211:Capsaicin