Summary
The effect of (R)α-methylhistamine (MH) and thioperamide (selective agonist and antagonist respectively of histamine H3 receptors) was examined in conscious gastric fistula dogs to investigate the role of histamine H3 receptors in the control of basal and stimulated gastric acid secretion. Intravenous infusion of MH at 0.3 and 0.6 μmol/kg/h caused a significant reduction of the 2-deoxy-d-glucose (2-DG)-stimulated acid output, maximal inhibition being 60%. The inhibitory effect of MH was counteracted by thioperamide (0.1 μmol/kg/h), which, by itself, did not modify the 2-DG-induced acid secretion. The increase in plasma gastrin levels induced by 2-DG was not significantly affected either by MH or by thioperamide. Under basal conditions MH (0.3 μmol/kg/h) did not induce any significant change in acid secretion and in plasma gastrin levels; by contrast, thioperamide (0.1 μmol/kg/h) produced a significant increase both in acid output and in plasma gastrin.
These results suggest that activation of H3 receptors can exert a negative control in stimulated acid secretion in conscious dogs, when cholinergic pathways to acid secretion are activated by 2-DG; moreover, the slight, but significant, stimulatory effect of thioperamide on basal acid output and basal plasma gastrin may be suggestive for a tonic inhibitory role of H3 receptors in the regulation of basal acid secretion, however, a nonspecific effect of this drug cannot be excluded.
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References
Arrang JM, Garbarg M, Schwartz JC (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptors. Nature 302:832–837
Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard M, Robba M, Schunack W, Schwartz JC (1987) Highly potent and selective ligands for histamine H3 receptors. Nature 327:117–123
Bado A, Dubrasquet M, Lewin MJM (1990) Evidence of histamine H3 receptors in the stomach: physiological role in gastric acid secretion. Gastroenterology 98:A17
Bado A, Hervatin F, Lewin MJM (1991a) Pharmacological evidence for histamine H3 receptor in the control of gastric acid secretion in cats. Am J Physiol 260:G631-G635
Bado A, Moizo L, Laigneau JP, Lewin MJM (1991b) Stimulation of aminopyrine accumulation and histamine release in isolated rabbit gastric glands by thioperamide, the histamine H3-receptor antagonist. Gastroenterolgy 100:A629
Bent S, Fehling U, Braam U, Schunack W, Schmutzler W (1991) The influence of H1, H2 and H3 receptors on the spontaneous and ConA induced histamine release from human adenoidal mast cells. Agents Actions 33:67–70
Bertaccini G, Coruzzi G (1992) Histamine receptors in the digestive system. In: Schwartz JC, Haas HL (eds) Receptor biochemistry and methodology: the histamine receptor, vol 16. Wiley-Liss, New York, pp 193–230
Coruzzi G, Bertaccini G, Schwartz JC (1991) Evidence that histamine H3 receptors are involved in the control of gastric acid secretion in the conscious cat. Naunyn-Schmiedeberg's Arch Pharmacol 343:225–227
Coruzzi G, Adami M, Bertaccini G (1992) Histamine H3 receptors are not involved in the regulation of rat gastric secretion. Pharmacology 44:190–195
Debas HT (1987) Peripheral regulation of gastric acid secretion. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 2nd ed. Raven Press, New York, pp 931–945
Gespach C, Fagot D, Emami S (1989) Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists. Eur J Clin Invest 19:1–10
Hervatin F, Dubrasquet M, Lewin MJM (1989) Histamine H3 receptors in the regulation of gastrin stimulated gastric acid secretion in conscious cat. Gastroenterology 96:A207
Ichinose M, Stretton CD, Schwartz JC, Barnes PJ (1989) Histamine H3 receptors inhibit cholinergic neurotransmission in guinea pig airways. Br J Pharmacol 97:13–15
Ishikawa S, Sperelakis N (1987) A novel class (H3) of histamine receptors on perivascular nerve terminals. Nature 327:158–160
Mengozzi G, Della Longa A, Martelli F, Soldani G (1988) Evidence for a regulatory role of alpha-2 receptors on gastric secretion and gastrin release in the dog. Pharm Res Commun 20:425–426
Molderings GJ, Weißenborn G, Schlicker E, Likungu LJ, Göthert M (1992) Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein by presynaptic histamine H3 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 346:46–50
Pile AJ, Smaje LH (1992) The H3 antagonist thioperamide inhibits the permeability effect of histamine in rat microvessels via an H1 receptor effect. Br J Pharmacol 105:210P
Sandvik AK, Lewin MJM, Waldum HL (1989) Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors. Br J Pharmacol 96:557–562
Soldani G, Del Tacca M, Martino E, Bartelloni A, Impicciatore M (1983) The involvement of the vagal pathway in the antisecretory effect of thyrotropin-releasing hormone on gastric secretion in the dog. J Pharm Pharmacol 35:119–121
Soldani G, Del Tacca M, Bernardini C, Martinotti E, Impicciatore M (1984) Evidence for two opposite effects of clonidine on gastric acid secretion in the dog. Naunyn-Schmiedeberg's Arch Pharmacol 327:139–142
Soll AH, Berglindh T (1987) Physiology of isolated gastric glands and cells: receptors and effectors regulating functions. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 2nd ed. Raven Press, New York, pp 883–909
Trzeciakowski JP (1987) Inhibition of guinea pig ileum contractions mediated by a class of histamine receptors resembling the H3 subtype. J Pharmacol Exp Ther 243:874–880
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Correspondence to G. Bertaccini at the above address
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Soldani, G., Mengozzi, G., Intorre, L. et al. Histamine H3 receptor-mediated inhibition of gastric acid secretion in conscious dogs. Naunyn-Schmiedeberg's Arch Pharmacol 347, 61–65 (1993). https://doi.org/10.1007/BF00168773
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DOI: https://doi.org/10.1007/BF00168773