SOMATOSTATIN EFFECTIVELY PREVENTS ETHANOL-INDUCED AND NSAID-INDUCED GASTRIC-MUCOSAL DAMAGE IN RATS

The interrelationship between somatostatin and its synthetic analog, s andostatin, with neuropeptides and inflammatory mediators, as well as their protection of gastric mucosal damage, were tested in rats. Rats were treated intragastrically with 1.0 ml of 96% ethanol with or witho ut intravenous or intraperitoneal coadministration of somatostatin (1. 0 muM/kg). Mucosal damage was also induced by the administration of ei ther indomethacin (30 mg/kg subcutaneously) with or without intravenou s sandostatin (10 mug/rat), given 30 min prior to damage induction. So matostatin levels in ethanol-damaged gastric mucosa were significantly lower than in control rats. Substance P and vasoactive intestinal pep tide (VIP) levels were significantly higher in the damaged mucosa in r ats treated with ethanol, as was the mucosal generation of leukotriene B4 (LTB4) and cysteinyl-containing leukotrienes. The coadministration of somatostatin with ethanol significantly reduced gastric mucosal in jury induced by ethanol alone. The protection of the mucosa was accomp anied by reduction of mucosal substance P and VIP levels, as well as t he generation of leukotrienes, an effect that was reversed by intraper itoneal or intravenous coadministration of somatostatin antagonist, cy clo-(7-aminoheptanoyl-PH-E-D-Trp-Lys-THR), 1.0 muM/100 g, with somatos tatin (1.0 muM/kg) and ethanol. When given by itself somatostatin sign ificantly reduced mucosal leukotriene generation compared with their g eneration in saline-treated rats. Sandostatin completely abolished gas tric mucosal damage induced by indomethacin administration. In rats tr eated with somatostatin and indomethacin, this effect was accompanied by reduction of mucosal leukotriene generation. Administration of sand ostatin to pylorus-ligated rats significantly reduced gastric acid out put. It is suggested that somatostatin may be involved in the pathogen esis of acute ethanol- and NSAID-induced gastric mucosal injury and th at part of its protective effect involves interrelationships with the neuropeptides, substance P and VIP, as well as inhibition of mucosal l eukotriene production.