AN UPDATE ON HISTAMINE H-3 RECEPTORS AND GASTROINTESTINAL FUNCTIONS

The distribution and functions of histamine H-3 receptors in the gastrointestinal tract is reviewed with particular reference to the effects on gastric acid secretion, mucosal protection, and intestinal motility. Histamine H-3 receptor activation has negative effects on acid secretion induced by indirect secretagogues in cats, dogs, and rabbits; less clear effects were found in rats. An inhibitory effect on histamine release induced by different stimuli was observed in rats, rabbits, and dogs after H-3 receptor agonists, thus supporting the idea that H-3 receptors occur in ECL cells. (R)-alpha-methylhistamine has a marked protective effect against gastric lesions induced by ethanol in rats, being slightly less effective against aspirin and stress. H-3 receptor activation decreases the intestinal motility induced by electrical stimulation in a variety of gut preparations, reducing both cholinergic and NANC neurotransmitter release. In this tissue the inhibitory effects mediated by histamine H-3 receptors seem to be coupled, via a G protein, to a restriction of Ca2+ access into the nerve terminal; other mechanisms, however, have been suggested in the gastric mucosa. Histamine H-3 receptors have already been subdivided into two receptor subtypes, H-3A and H-3B, the former being the subtype predominant in the gastrointestinal tissue. The increasing availability of selective agonists and antagonists of H-3 receptors will unravel possible novel actions and physiological roles of histamine.