The relationship between the secretion of gastrin, somatostatin and GRP (gastrin releasing polypeptide) from the antrum

S5 EFFECTS OF GASTRIN RELEASINGPEPTIDE (GRP) AND ~ALOGS ON GASTRIC ACID SECRETION. T.E.Solomon, Truman VA Hospital and University of Missouri, Columbia, Missouri, USA I previously reported that bombesin and bombesin nonapeptide were strong releasers of gastrin in rats but that neither peptide stimulated gastric acid secretion and both peptides inhibited pentagastrin and histamine-lnduced acid secretion in rats (Gastroenterology 80:1289,1981). In the present study I examined the effect of GRP and analogs on acid secretion. Rats were prepared with a gastric fistu|a and intravenous catheter; they were placed in Bollman restraining cages and studied on the f i r s t and second days after surgery. GRP(I-27), GRP(14'27), l i t o r i n , and ranatensin (all synthetic, obtained from Peninsula Laboratory) wereodissolved in a solution of I% (w/v) albumin in 0.15 M NaCl and stored at -20 until use. Groups of 6 to IO rats received increasing doses (0.37, l . l , 3.3, lO ~g/kg-h) of each peptide (each dose for 30 min) either alone or with a background infusion of a submaximal dose of pentagastrin (4 ~g/kg-h). Control data were available from large numbers of rats which had received no peptides or pentagastrin alone. None of the GRP analogs stimulated gastric acid secretion above basal levels. GRP(l-27) and GRP(14-27) each inhibited basal acid secretion (maximal inhibition 57% and 73% respectively). Each of the 4 GRP analogs inhibited pentagastrin-induced acid secretion (increment over basal) by I00%. The most potent analog on a molar basis was GRP (ID50 396 pmol/kg-h). Acid secretion returned to control levels within 30 minutes after stopping the infusion of GRP analogs. These data indicate peptides in the GRP-bombesin family are strong inhibitors of acid secretion in rats. The mechanism for this inhibition is not known. THE RELATIONSHIP BETWEENTHE SECRETION OF GASTRIN, SOMATOSTATINAND GRP (GASTRIN RELEASING POLYPEPTIDE) FROMTHE ANTRUM. J.J. Holst, S. Knuhtsen, U. Knigge, S.L. Jensen and O.V. Nielsen. I n s t i t u t e of Medical Physiology C, The Panum I n s t i t u t e , and Department of Surgery C, Rigshospitalet, University of Copenhagen, Denmark. The porcine antrum was isolated (together with the pancreas) and perfused in v i t r o with an a r t i f i c i a l medium supplemented with erythrocytes. The vagal innervation was preserved. Effluent was collected from a n t r a l , v e i n s , and analyzed for somatostatin, gastrin and GRP ("mammalian bombesin") using an assay developed against synthetic porcine GRP 1-27 (Peninsula): antisera were raised against GRP-albumin-conjugate, 125-I-GRP was labelled using the stoichiometric chloramin-T method. Separation: plasma-coated charcoal. S e n s i t i v i t y better than 2 pmol/l. Vagal stimulation increased pancreatic exocrine secretion 80-fold, and caused strong antral contractions. Gastrin output increased 2-5 f o l d , and somatostatin output decreased to 58% (p = 0.01, n = 7). Basal e f f l u e n t levels of GRP varied between zero and 15 pM, and vagal stimulation caused at least 10fold increases in GRP output. Intraluminal HCI (20 ml 0.1 M) i n h i b i t e d gast r i n release to 70% and stimulated somatostatin release to 145% (P : 0.02), whereas the already low levels of GRP were suppressed below detection l i m i t . I n t r a a r t e r i a l pentagastrin at 10-8 mol/l increased somatostatin by 149-200% and inhibited GRP output. Thus, the stimulatory peptide GRP and the i n h i b i t o r y peptide somatostatin were both released from the porcine antrum, and t h e i r release was influenced by vagal a c t i v i t y and luminal a c i d i t y in a pattern which corresponds to the effects of these stimuli on antral gastrin output. I t is suggested that antral somatostatin and GRP are push-pull controllers of antral gastrin release.