Rapid onset of (R)-alpha-methylhistamine protection in response to ethanol-induced histologic damage in rat gastric mucosa.

The influence of pretreatment with (R)-alpha-methylhistamine, selective agonist of histamine H3 receptors, has been investigated on gastric mucosal lesions at different time intervals, from 5 to 60 minutes, after administration of absolute ethanol in the rat. The amount and depth of lesions were quantitatively evaluated by light microscopy. In rats pretreated with (R)-alpha-methylhistamine, the integrity of the mucosa was preserved in approximately 80% of the total mucosal length measured despite ethanol challenge. Prevention of lesion formation was as great at 5 min after ethanol administration as at 60 min. When present, damage involved mainly superficial mucosa and lesions extending deeply into the gland region were evident in 1-2.5% of the total mucosa. Present findings indicate that mechanisms by which (R)-alpha-methylhistamine operates enable the mucosa to counteract damage just from the moment of exposure to ethanol and that protection is exerted both on surface and pit cells and on gastric glands.