Role of vasoactive intestinal peptide (VIP) in pathogenesis of ethanol-induced gastric mucosal damage in rats.
To elucidate the possible role of vasoactive intestinal peptide (VIP) in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 ml 96% ethanol with or without intravenous or intraperitoneal coadministration of VIP (1 nmol/liter to 1 mumol/liter/100 g). VIP was found to double the mean lesion area when compared with that induced by ethanol alone (P < 0.05), an effect that was prevented by VIP antagonist (1 mumol/liter/100 g). A substance P antagonist (1 mumol/liter/100 g) also reduced the extent of gastric damage induced by coadministration of VIP and ethanol. VIP antagonist or substance P antagonist significantly reduced ethanol-induced gastric mucosal damage. Gastric mucosal levels of LTB4, LTC4, VIP, and substance P were significantly increased in ethanol-treated rats as compared with saline-treated animals (P < 0.05). The augmentation of ethanol-induced damage by VIP was associated with increased gastric mucosal levels of LTB4. In VIP-treated rats, gastric mucosal levels of substance P were found to be significantly increased compared with control rats (P < 0.05). Administration of VIP to pyloric-ligated rats significantly increased gastric acid output and blood pepsinogen A levels as compared with saline treated rats (P < 0.05). Ketotifen, a mast cell stabilizer (100 micrograms/100 g), administered orally 30 min before damage induction by ethanol, with or without VIP, totally abolished the damage of the surface epithelium of the entire gastric mucosa and significantly reduced the mucosal levels of LTC4 and LTB4 (P < 0.05). It is suggested that VIP is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Karmeli
F
F
Department of Medicine, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Eliakim
R
R
Okon
E
E
Rachmilewitz
D
D
D000208:Acute Disease; D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007665:Ketotifen / Q000494:pharmacology; D015289:Leukotrienes / Q000032:analysis; D008297:Male; D051381:Rats; D013272:Stomach Diseases / Q000209:etiology* / Q000473:pathology; D013373:Substance P / Q000037:antagonists & inhibitors; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D015289:Leukotrienes; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D000431:Ethanol; D007665:Ketotifen