HMT regulates histamine-induced glycoconjugate secretion from human airways in vitro

To determine whether histamine N-methyltransferase (HMT) regulates mucus glycoprotein (MGP) secretion from airways, we examined the effect of an HMT inhibitor, SKF 91488, on MGP secretion from human airways in vitro. MGP secretion from human airway explants (with epithelium) and isolated submucosal glands was estimated by measuring trichloroacetic acid (TCA) precipitable glycoconjugates using secretory indices. Histamine induced significant MGP secretion from both explants and isolated glands. Pretreatment with SKF 91488 significantly inhibited histamine-induced secretion from explants, while it did not alter significantly the secretion from isolated glands. H1-blocker significantly reversed the inhibition by SKF 91488 of the secretion from explants, while H2-blocker abolished histamine-induced secretion from both explants and isolated glands. Prostaglandin E2 (PGE2) significantly inhibited histamine-induced secretion from isolated glands. The inhibitory action of SKF 91488 in airway explants was blocked by indomethacin and was significantly reduced by a prostanoid EP4 receptor antagonist (AH23848B). These findings suggest that HMT regulates MGP secretion from human airway submucosal glands through an interaction with epithelial cells which involves the release of PGE2.