Morphological characteristics of enteric neurons projecting from the small intestine and colon to the cranial mesenteric ganglion of the pig

262 MOLECULAR BASIS FOR SOMATOSTATIN ACTION. A. Todisco, V. Campbell, C. Dickinson, J. Del Valle, T. Yamada. Departments of Internal Medicine and Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan. Somatostatin is known to have an inhibitory effect on a wide variety of gastrointestinal functions. The molecular mechanisms of somatostatin action have been investigated extensively but understood only partially. Recent studies have shown that somatostatin can inhibit gene transcription directly. In view of their critical importance in induction of gene expression, we examined whether the universal inhibitory action of somatostatin might be mediated by inhibiton of immediate early genes. Accordingly, we examined the effects of somatostatin on c-fos gene expression using isolated gastric parietal cells and ceils derived from a rat pituitary adenoma cell line (GH3) that have been shown to have TRH, VIP, and somatostatin receptors. Canine parietal cells were dispersed by collagenase and EDTA treatment and further isolated by counterflow elutriation. Immediately after isolation the cells were incubated with either 10"~M carbachol or 104M histamine alone or in combination with 10-TM somatostatin. GH3 cells were grown for 36 h in serum free medium prior to the administration of 10-TM VIP, 10-TM TRH,10-4M DBcAMP or 20% fetal calf serum alone, or in combination with 10-TM somatostatin. Ceils were harvested after 30 rain of incubation with the test substances and total RNA was extracted, c-Fos specific m-RNA was determined by Northern blot hybridization using a 32P-labeled c-DNA probe and autoradiograms were quantified by scanning densitometry, c-Fos gene expression in both parietal and GH3 cells was stimulated with agents known to act via accumulation of cAMP and increase in intracellular calcium and somatostatin treatment inhibited this response by 50-70%. We performed additional experiments to examine whether the effects of somatostatin were mediated by pertussis toxin sensitive inhibitory GTP binding proteins. Pertussis toxin pretreatment (200ng/ml) reversed somatostatin inhibition of c-fos gene expression stimulated by TRH, VIP, DBcAMP or serum. Our observations support the hypothesis that somatostatin's universal inhibitory action could be mediated, at least in part, by inhibition of expression of early response genes. This effect appears to be pertussis toxin-sensitive and is likely to involve an inhibitory GTP binding protein.

SOMATOSTATIN IN THE MANAGEMENT OF GASTROINTESTINAL FISTULAS AJ Torres; JL Landa; M Moreno; JM Arguello; G Silecchia; M Gomez: F Hernandez; J Jover; E Moreno; JL Balibrea. HUSC (Madrid); 12 Octubre (Madrid) To evaluate the effectiveness of treatment with total parenteral nutrition (TPN) alone (group A) or combined with continuous intravenous infusion of somatostatin (group B) in postoperative gastrointestinal fistulas, a multicenter, controlled and prospective randomized trial was designed. We present the results of obtained after the evaluation of 40 cases (group A, n=20; group B, n=20). No significant differences among these treatment schedules were observed in the percentage of closure of fistulas (group A, 81.25%; group B, 85%), but patients treated with TPN plus somatostatin had the fistulas close within a significantly shorter period of time. Moreover this treatment was associated with a significantly lower morbidity. These preliminary results indicate that somatostatin is a useful therapeutic compliment in the conservative treatment of patients with gastrointestinal fistulas.