The effect of drugs and secretagogues on the biosynthesis of gastric mucins

Gastric mucosal glycoproteins were separated into three well-defined fractions: secreted mucin in vivo, adherent to cells, Fraction I; soluble mucin secreted during incubation in vitro, Fraction II; and a third, Fraction III released solely by pronase digestion (cell bound or intracellular mucin). 14C-U-D-glucose and 35SO 4 incorporation into glycoprotein fractions II and III was studied during a 4-hr incubation period in vitro, of mucosal scrapings, freed from Fraction I, from rats treated in vivo, with secretin, histamine, aspirin and atropine. The effect of in vitro added puromycin and actinomycin was also studied. Secretin decreased and histamine increased the total amount of protein and glycoprotein in Fraction II. Histamine inhibited incorporation of glucose into this fraction, to a moderate extent. Secretin had no effect on incorporation. Per oral aspirin, administered for 15 min, decreased levels of secreted mucin Fraction I, and strongly inhibited glucose incorporation in Fraction III. Parenterally administered aspirin and atropine decreased mucin secretion in vivo (Fraction I) but activated glucose incorporation slightly in Fraction II and strongly in Fraction III. Puromycin and actinomycin added in vitro to the mucosal scrapings inhibited strongly glucose incorporation in Fraction III, but did not inhibit incorporation in Fraction II. This indicates the existence of two separate phases of mucin biosynthesis and secretion, both necessitating glucose incorporation, but only the first one being sensitive to puromycin and actinomycin. 35SO 4 incorporation was strongly inhibited by all drugs studied. Sulphation of mucins appears to be much more sensitive to drug action than mucin biosynthesis itself. The above results indicate that the described system is suitable for the study in vitro of the time sequence and mechanisms of drug action.