Histamine H3-receptor antagonists inhibit gastroprotection by (R)-α-methylhistamine in the rat

1 (R)-alpha-methylhistamine, a selective agonist of hist amine H-3 receptors, is capable of protecting the gastric mucosa against differently acting damaging agents. The objective of the present study was to determine whether H-3 receptors mediate its protective action in the rat. 2 Gastric mucosal lesions were induced intragastrically (i.g.) by 0.6 N HCl, 1 mi rat(-1). (R)-alpha-methylhistamine, 100 mg kg(-1) i.g., substantially reduced the severity of macroscopically and histologically assessed damage caused by concentrated acid. Prior treatment with highly selective H-3- receptor antagonists, ciproxifan (0.3, 1 and 3 mg kg(-1) i.g.) and clobenpropit (3, 10 and 30 mg kg(-1) i.g.), dose-dependently inhibited the protection exerted by (R)-alpha-methylhistamine up to a complete reversal. When given alone at high doses, both antagonists tended to worsen the HCl-induced histologic damage. 3 During basal conditions, (R)-alpha-methylhistamine, 100 mg kg(-1) i.g., caused a significant increase in titratable acidity of the gastric juice. Prior treatment with ciproxifan (3 mg kg(-1) i.g.) and clobenpropit (30 mg kg(-1) i.g.) did not alter the secretory response to (R)-alpha-methylhistamine. Clobenpropit alone, but not ciproxifan, increased the volume of gastric juice, and both compounds alone had no effect on titratable acid. 4 Present findings support evidence that H-3 receptors an actively involved in the maintenance of gastric mucosal integrity, with no apparent role in the regulation of basal gastric acid secretion.