devazepide and Stomach-Ulcer

Bombesin has been shown to have trophic effects on the gastrointestinal tissue. Bombesin has direct mitogenic effects besides stimulating release of gastric hormones. The aim of this study was to investigate the effect of bombesin in hemorrhagic shock-induced stress ulcers in rats, and the role of cholecystokinin (CCK) receptors in this activity. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g b.w. of rats. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase activity and gastric protein oxidation levels were determined. When given before the hemorrhage, subcutaneous bombesin (10 microg/kg) reduced macroscopically gastric ulcer index (p < 0.05). Blockade of CCK-A receptors with intraperitoneal MK-329 (1 mg/kg) did not reverse bombesin-induced gastroprotection. Blockade of CCK-B receptors with intraperitoneal L-365,260 (25 mg/kg) reversed bombesin-induced gastroprotection. Blockade of the two receptors resulted in no gastroprotection at all. It is concluded that bombesin treatment attenuated hemorrhagic shock-induced stress ulcers in rats via CCK receptors.

Topics: Animals; Benzodiazepinones; Bombesin; Devazepide; Gastric Mucosa; Hormone Antagonists; Male; Phenylurea Compounds; Rats; Rats, Wistar; Receptors, Cholecystokinin; Shock, Hemorrhagic; Stomach Ulcer

We have investigated the effect of intravenous injection of cholecystokinin-8 (CCK-8) and other peptides on gastric lesion formation in response to an intragastric perfusion with 25% ethanol in rats anaesthetized with urethane. 2. Intravenous injection of CCK-8 (50-100 nmol kg-1), but not bombesin (1-100 nmol kg-1), calcitonin gene-related peptide (1-50 nmol kg-1), neurokinin A (1 mumol kg-1) or substance P (100 nmol kg-1), induced protection against gastric haemorrhagic lesions produced by ethanol. 3. The CCKA-antagonist L-364,718 (2.45 mumol kg-1, i.v.) increased the lesion index induced by ethanol and reversed the protective effect of CCK-8 (50 nmol kg-1, i.v.). The CCKB-antagonist L-365,260 (5 mumol kg-1, i.v.) and a lower dose of L-364,718 (0.25 mumol kg-1, i.v.) were ineffective. 4. The gastric protective effects afforded by CCK-8 (50 nmol kg-1, i.v.) were not observed in vagotomized-rats and were reduced by capsaicin pretreatment. In capsaicin-pretreated rats there was a worsening of gastric lesions induced by ethanol-perfusion as compared to those observed in vehicle-pretreated rats. 5. These results demonstrate that the mucosal protective effect of CCK-8 involves, at least in part, the activation of CCKA-receptors and is mediated by vagal capsaicin-sensitive fibres.

Topics: Animals; Benzodiazepinones; Capsaicin; Devazepide; Ethanol; In Vitro Techniques; Male; Neurons; Phenylurea Compounds; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Sensory Deprivation; Sincalide; Stomach Ulcer; Vagotomy; Vagus Nerve