The effects of indomethacin and prostaglandins E2 and F2 alpha on canine tracheal mucus generation.

The effects of prostaglandins on respiratory smooth muscle are well known; however, their role in mucus generation has received little attention. This investigation was undertaken to study the actions of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) on secretion and synthesis of respiratory mucus glycoproteins. The method employed canine tracheal explants; radiochemical precursors were used in the culture media for labelling and quantitation of the secreted glycoproteins. Glycoprotein secretion was not significantly influenced by PGE2 (1 x 10(-10) to 1 x 10(-3) M) or PGF2 alpha (1 x 10(-8) to 1 x 10(-4) M). However, PGF2 alpha (1 x 10(-3) M and 1 x 10(-2) M), significantly stimulated glycoprotein secretion. The mechanism may have involved a contractile effect on myoepithelial cells of the submucosal glands. Synthesis of glycoproteins was significantly inhibited by PGF2 alpha (1 x 10(-5) M), indomethacin (1 x 10(-6) M), and the combination PGF2 alpha (1 x 10(-5) M)/indomethacin (1 x 10(-6) M). PGE2 (1 x 10(-5) M) and arachidonic acid (1 x 10(-5) M) were without effect. These data suggested that indomethacin inhibited glycoprotein synthesis by a mechanism other than an action on prostaglandin synthetase. In addition, because these agents inhibited synthesis of glycoproteins which were labeled with 3H-glucosamine, 35S-sulfate, and 14C-serine, it appears that their action was primarily upon synthesis of the protein core.