J. Tamaoki et al., HISTAMINE H-2 RECEPTOR-MEDIATED AIRWAY GOBLET CELL SECRETION AND ITS MODULATION BY HISTAMINE-DEGRADING ENZYMES, Journal of allergy and clinical immunology, 99(2), 1997, pp. 233-238
Background: Airway goblet cell hypersecretion may contribute to the pa
thophysiology of asthma. However, it is unknown whether histamine affe
cts goblet cell secretion and, if so, which subtype of histamine recep
tor is involved and whether endogenous histamine-degrading enzymes mod
ulate these actions. Methods: We morphometrically assessed goblet cell
secretion in the guinea pig trachea stained with alcian blue and peri
odic acid Schiff stains by measuring the mucus score, which wash inver
sely related to the degree of mucus glycoprotein discharge. Results: I
nhalation of histamine caused a dose-dependent decrease in mucus score
, an affect that was inhibited by pretreatment with the H-2-receptor a
ntagonist cimetidine but not with the H-1-receptor antagonist mepyrami
ne or the H-3-receptor antagonist thioperamide. Inhaled Dimaprit, a se
lective H-2-receptor agonist, likewise decreased mucus score; whereas
stimulation of H-1- and H-3-receptors with 2-methylhistamine and (R)-a
lpha-methylhistamine, respectively, had no effect. Pretreatment with t
he histamine N-methyltransferase inhibitor SKF 91488, but not the diam
ine oxidase inhibitor aminoguanidine, potentiated the dose-dependent e
ffect 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 hist
amine methyltransferase activity in the tracheal mucosa was 29 times h
igher than diamine oxidase activity. Conclusion: These findings sugges
t that histamine stimulates airway goblet cell secretion through H-2-r
eceptors and that this effect may be modulate principally by endogenou
s histamine methyltransferase through a degradation of histamine.