Abstract
This study was undertaken to determine gastric acid response to histamine applied topically to the mucosal surface and to examine the local effect of ranitidine, a histamine H2-receptor antagonist, on the gastric acid response to histamine. Histamine applied to the Heidenhain pouch (HP) mucosa resulted in a slight and dose-dependent stimulation of acid secretion without affecting acid secretion from the main stomach. Ranitidine given into the HP caused dose-dependent inhibition of the HP response to topical or intravenous histamine without affecting the acid response of the main stomach and without any significant change in the serum ranitidine level. Ranitidine applied to the main stomach with the pylorus occluded inhibited histamineinduced acid secretion also without any increase in the serum ranitidine level. This inhibition was about 30% of that obtained with the same dose of ranitidine given into the stomach with the pylorus left open during the experiment. This study provides evidence that topical hsitamine is a weak stimulant of gastric secretion and that topical ranitidine is capable of local inhibition of the acid response to both topical or intravenous histamine.
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References
W. Feldberg andG.W. Harris,Distribution of histamine in the mucosa of the gastrointestinal tract of the dog, J. Physiol.120, 352–364 (1953).
O.B. Reite,Comparative physiology of histamine, Physiol. Rev.52, 778–819 (1972).
W. Lorenz, E. Matejka, A. Schmal, W. Seidel, H.J. Rieman, R. Uhlig andS. Mann,A phylogenetic study on the occurrence and distribution of histamine in the gastrointestinal tract and other tissues of man and various animals, Comp. Gen. Pharmac.4, 229–250 (1973).
A.H. Soll, K. Lewin andM.A. Beaven,Isolation of histamine-containing cells from canine fundic mucosa, Gastroenterology77, 1283–1290 (1979).
F.C. MacIntosh,Histamine as a normal stimulant of gastric secretion, Q.J. Exp. Physiol.28, 87–98 (1938).
C.F. Code,Histamine and gastric secretion: a later look, 1955–1965, Fedn Proc.24, 1311 (1965).
E.L. Blair, The question of the release of histamine by gastrin. InGastrin, p. 225. (Ed.M.I. Grossman) UCLA Forum in Med. Sciences, Los Angeles 1966.
J.W. Black, W.A.M. Duncan, G.J. Durant, C.R. Ganellin andE.M. Parsons,Definition and antagonism of histamine H 2-receptors. Nature236, 385–390 (1972).
C.F. Code, W.E.R. Green, J.C. Kennedy, H.D. Ritchie andJ.F. Schlegel,Metabolism of histamine in secreting intact and isolated canine stomach, Am. J. Physiol.230, 219–227 (1976).
W. Lorenz, H. Troidl, H. Barth, H. Rohde, S. Schulz, H. Becker, P. Dormann, A. Schmal, J. Kusche andR. Meyer, Stimulus-secretion coupling in the human and canine stomach: role of histamine. InStimulus Secretion Coupling in the Gastrointestinal Tract, p. 177. (EdsR.M. Case andH. Goebell) MTP Press Ltd, Lancaster 1976.
R.K.S. Lim, A.C. Ivy andJ.E. McCarthy, Contributions to the physiology of gastric secretion. InGastric secretion by local (mechanical and chemical) stimulation, Am. J. Physiol.15, 13–68 (1925).
F. Holander andA. Schapira,Gastric response to topical histamine; subcutaneous dose-response relation, Am. J. Physiol.205, 625–630 (1963).
M. Cieszkowski, S.J. Konturek, W. Obtulowicz andJ. Tasler,Chemical stimulatory mechanism in gastric secretion, J. Physiol.246, 143–157 (1975).
D.C. Carter andM.I. Grossman,Effect of luminal pH on acid secretion from Heidenhain pouches evoked by topical and parenteral stimulants, J. Physiol.281, 227–237 (1978).
H.T. Debas, S.J. Konturek, J.H. Walsh andM.I. Grossman,Proof of a pyloro-oxyntic reflex for stimulation of acid secretion, Gastroenterology66, 526–532 (1974).
I. Fellows, W.N. Jenner, L.E. Martin andB.A. Willoughby,The development of a radioimmunoassay for ranitidine in biological fluids, Br. Pharm. Soc. Meeting, London 1980.
M. Dworetzky andC.F. Code,Passage of histamine across the wall of the small bowel of guinea pigs, Am. J. Physiol.166, 462–000 (1951).
S.A.M. Cross,Localization of histamine and histamine H 2-receptor antagonists in the gastric mucosa, Histochem. J.9, 619–644 (1977).
D.R. Bristow, J.R. Hare, J.R. Hearn andL.E. Martin,Radioligand binding studies using [3H]-Cimetidine and [3 H]-ranitidine, Br. Pharm. Soc. Meeting, Aberdeen 1980.
D.B. Norris, T.J. Rising, S.E. Warrander andT.P. Wood, [3 H]-Cimetidine binding in guinea-pig gastric mucosa, Br. Pharm. Soc. Meeting, Aberdeen 1980.
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Konturek, S.J., Cieszkowski, M., Kwiecień, N. et al. Gastric acid response to topical or intravenous histamine and topical H2-receptor blockade in dogs. Agents and Actions 11, 437–441 (1981). https://doi.org/10.1007/BF02004703
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DOI: https://doi.org/10.1007/BF02004703