Histamine H-2 receptor-mediated airway goblet cell secretion and its modulation by histamine-degrading enzymes

Background: Airway goblet cell hypersecretion may contribute to the pathophysiology of asthma. However, it is unknown whether histamine affects goblet cell secretion and, if so, which subtype of histamine receptor is involved and whether endogenous histamine-degrading enzymes modulate these actions. Methods: We morphometrically assessed goblet cell secretion in the guinea pig trachea stained with alcian blue and periodic acid Schiff stains by measuring the mucus score, which wash inversely related to the degree of mucus glycoprotein discharge. Results: Inhalation of histamine caused a dose-dependent decrease in mucus score, an affect that was inhibited by pretreatment with the H-2-receptor antagonist cimetidine but not with the H-1-receptor antagonist mepyramine or the H-3-receptor antagonist thioperamide. Inhaled Dimaprit, a selective H-2-receptor agonist, likewise decreased mucus score; whereas stimulation of H-1- and H-3-receptors with 2-methylhistamine and (R)-alpha-methylhistamine, respectively, had no effect. Pretreatment with the histamine N-methyltransferase inhibitor SKF 91488, but not the diamine oxidase inhibitor aminoguanidine, potentiated the dose-dependent effect of histamine on goblet cell secretion, causing a decrease in the concentration of inhaled histamine required to produce a half-maximal effect from 0.80 +/- 0.12 to 0.48 +/- 0.09 mg/ml (p < 0.01). The histamine methyltransferase activity in the tracheal mucosa was 29 times higher than diamine oxidase activity. Conclusion: These findings suggest that histamine stimulates airway goblet cell secretion through H-2-receptors and that this effect may be modulate principally by endogenous histamine methyltransferase through a degradation of histamine.