The short term effect of peripherally administered brain-gut peptides on gastric acid secretion in rats
- 22 Downloads
Certain brain gut-peptides are known to either stimulate or inhibit gastric acid secretion in several species after direct injection into the central nervous system. However there is inconsistency of published results on the gastric acid secretory response to some of these peptides after peripheral administration in different experimental systems. Seven peptides, namely neurotensin (NT), substance P, cholecystokinin (CCK), thyrotropin releasing hormone (TRH), human calcitonin (hCT), rat calcitonin-gene-related peptide (rCGRP) and bombesin, all known to modulate gastric acid secretion after central administration, were initially screened for activity after peripheral (subcutaneous) injection of 10 μg/kg body weight in a single rat model. Peptides showing an effect were retested at lower doses. Despite the inherent variability of the gastric acid secretory response in the non-anaesthetized pylorus ligated rat, a standardized experimental design confirmed that reproducible and statistically valid results could be obtained. The technical feasibility of using a one hour collection period as might be appropriate for short acting peptides was demonstrated by the significant dose dependent inhibitory activity of salmon calcitonin. In this model, NT and substance P had no significant effect on either volume or concentration of acid secreted, CCK showed a slight stimulation of acid output, and TRH, hCT, rCGRP and bombesin all inhibited acid output; CGRP and bombesin were active at 10 and 100-fold lower doses. The potent and inhibitory activity of bombesin in this system is in disagreement with other publications reporting no effect or variable stimulatory effect in rats. Time and dose dependent responses in our rat system indicate that this apparent discrepancy may be explained by the short duration of action of bombesin.
KeywordsCalcitonin Gastric Acid Secretion Acid Output Cholecystokinin Thyrotropin Release Hormone
Unable to display preview. Download preview PDF.
- J. E. Morley, A. S. Levine and S. E. Silvis,Central regulation of gastric acid secretion: the role of neuropeptides. Life Sci.31, 300–410 (1982).Google Scholar
- W. E. H. Doepfner and U. Briner,Calcitonin and gastric secretion. InCalcitonin 80. pp. 123–135 (Ed. A. Pecile). Excerpta Medica, Amsterdam 1980.Google Scholar
- K. N. Sharma, S. Dua and B. K. Anand,Effect of hypothalamic lesions on experimental gastric ulceration in rats. Indian J. Med.51, 708–715 (1963).Google Scholar
- S. Rosell,Substance P and neurotensin in the control of gastro intestinal function. InPeptides: Integrators of cell and tissue function. pp. 147–162 (Ed. F. E. Bloom) Raven Press, New York 1980.Google Scholar
- K. Yokotani and M. Fujiwara,The effects of substance P on cholinergically stimulated gastric acid secretion and mucosal blood flow in rats. J. Pharm. & Exp. Therapeutics232, 826–830 (1985).Google Scholar
- M. Azria,The calcitonins. Physiology and Pharmacology, Karger, Basel 1988.Google Scholar
- G. Bertaccini, V. Erspamer and M. Impicciatore,The actions of bombesin on gastric secretion of the dog and the rat. Br. J. Pharmac.49, 437–444 (1973).Google Scholar
- J. W. Du Val, B. Saffouri, G. C. Weir, J. H. Walsh, A. Arimura and G. M. Makhlouf,Stimulation of gastrin and somatostatin secretion from the isolated rat stomach by bombesin. Am. J. Physiol.214 (Gastrointest. Liver Physiol.4), G242-G247 (1981).Google Scholar
- Y.-S. Guo, M. Lester, C. W. Cooper, G. H. Greeley Jr., J. C. Thompson and P. Singh,Effect of gastrin releasing peptide analogues on gastrin and somatostatin release from isolated rat stomach. Am. J. Physiol.253 (Gastrointest. Liver Physiol.16), G206-G210 (1981).Google Scholar