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Somatostatin partially mediates CGRP-induced inhibition of gastric acid secretion in anesthetized rats
120 55 SIALOADENECTOMY S E L E C T I V E L Y I N C R E A S E S RAT G A S T R I C C A L C I T O N I N GENE-RELATED PEPTIDE: INTERACTION WITH CAPSAICIN-SENSITIVE AFFERENTS D. RENZI I, S. EVANGELISTA 2, C. SURRENTI 1 and C.A. MAGGI 3, IDept. ~lin. Pathophysiol., Gastroenterology Unit, V. le Morgagni, 85, Malesci Res. Lab.,3Menarini Res. Lab., Florence, ITALY. Sensory denervation induced by s y s t e m i c pretreatment with c a p s a i c i n and s i a l o a d e n e c t o m y h a v e b e e n shown to i n f l u e n c e gastric acid secretion (GAS) and ulcer formation. This effect is d e t e r m i n e d by v a s o d i l a t i n g p e p t i d e s c o n t a i n e d in c a p s a i c i n sensitive primary afferents (CSPA) and by epidermal growth factor (EGF) mainly produced by the salivary complex. In this study, we have investigated the possible interaction between these two r e g u l a t o r y s y s t e m s on GAS m e a s u r e d in p y l o r u s - l i g a t e d rats. Sialoadenectomized (SALX) rats showed a decrease in GAS and an increase in g a s t r i c calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) as compared to sham-operated animals. The increase in gastric content of CGRP was selective, since gastric vasoactive intestinal polypeptide (VIP), contained in intrinsic neurons of rat stomach, w~s unaffected in SALX rats. Capsaicin pretreatment (50+100 mg Kg -± in two days) significantly decreased gastric CGRP-LI in both sham- and SALX-operated rats and increased acid concentration and output only in SALX animals. In t h i s l a t t e r case the c o n c o m i t a n t a b s e n c e of two p o t e n t endogenous antisecretory agents (CGRP and EGF) may contribute to the observed hypersecretion. These findings provide the evidence for a functional interaction between t w o mayor systems regulating gastric acid secretion and protection against ulcerogenic stimuli.
56 SOMATOSTATIN PARTIALLY MEDIATES CGRP-INDUCED INHIBITION OF GASTRIC ACID SECRETION IN ANESTHETIZED RATS K.C. KENT LLOYD, HELEN C. WONG, AND JOHN H. WAI.SH Center for Ulcer Research and Education, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California, USA. In anesthetized rats, close-arterial injection of CGRP potently inhibits gastric acid secretion and causes release of endogenous somatostatin. In order to determine the amount of CGRP-induced inhibition of acid secretion that is mediated by somatostatin, we performed in vivo immunoneutralization of somatostatin using a somatostatin monoclonal antibody. Gastric acid secretion was measured by continuous intragastric titration to pH 7 through intragastric cannula in pylorus-ligated, fasted adult male rats anesthetized with thiopemal (60 mg/kg, i.p.). Basal acid output was significantly increased after i.v. administration of somatostatin monoclonal antibody #607 (2 mg; n=6), but was unaffected by administration of either CGRP monoclonal antibody #4901 (2 rag; n=6) or KLH (control) monoclonal antibody (2 mg; n= 10). CGRP (5 nmol/kg, 30 #1) injected through a catheter in the splenic artery close to the stomach inhibited pentagastrin (20 ug/kg/h) -stimulated acid secretion by 60% compared to vehicle (0.1% canine serum albumin in saline). Intravenous administration of CGRP monoclonal antibody reversed this inhibition by 97%, whereas 49% of inhibition was blocked by somatostatin monoclonal antibody. CONCLUSIONS: A substantial part of CGRP-induced inhibition of acid secretion is mediated by somatostatin. Since all CGRP in the rat stomach is of extrinsic sensory origin, these results imply visceral afferent neural regulation of endocrine cell function.
56 SOMATOSTATIN PARTIALLY MEDIATES CGRP-INDUCED INHIBITION OF GASTRIC ACID SECRETION IN ANESTHETIZED RATS K.C. KENT LLOYD, HELEN C. WONG, AND JOHN H. WAI.SH Center for Ulcer Research and Education, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California, USA. In anesthetized rats, close-arterial injection of CGRP potently inhibits gastric acid secretion and causes release of endogenous somatostatin. In order to determine the amount of CGRP-induced inhibition of acid secretion that is mediated by somatostatin, we performed in vivo immunoneutralization of somatostatin using a somatostatin monoclonal antibody. Gastric acid secretion was measured by continuous intragastric titration to pH 7 through intragastric cannula in pylorus-ligated, fasted adult male rats anesthetized with thiopemal (60 mg/kg, i.p.). Basal acid output was significantly increased after i.v. administration of somatostatin monoclonal antibody #607 (2 mg; n=6), but was unaffected by administration of either CGRP monoclonal antibody #4901 (2 rag; n=6) or KLH (control) monoclonal antibody (2 mg; n= 10). CGRP (5 nmol/kg, 30 #1) injected through a catheter in the splenic artery close to the stomach inhibited pentagastrin (20 ug/kg/h) -stimulated acid secretion by 60% compared to vehicle (0.1% canine serum albumin in saline). Intravenous administration of CGRP monoclonal antibody reversed this inhibition by 97%, whereas 49% of inhibition was blocked by somatostatin monoclonal antibody. CONCLUSIONS: A substantial part of CGRP-induced inhibition of acid secretion is mediated by somatostatin. Since all CGRP in the rat stomach is of extrinsic sensory origin, these results imply visceral afferent neural regulation of endocrine cell function.