Arachidonic acid stimulates mucin secretion in prairie dog gallbladder

Mucin glycoprotein secretion from prairie dog gallbladder explants was studied in 24-h organ culture using [3H]glucosamine as a precursor. Indomethacin caused a reversible dose-dependent inhibition of both mucin release (50% inhibition between 10(-6) and 10(-5) M indomethacin) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release (66% inhibition at 10(-7) M). Sepharose 4B chromatography of secreted [3H]-glucosamine-labeled glycoproteins revealed that indomethacin inhibited release of a high-molecular (greater than 10(6) daltons) mucin-type glycoprotein. Addition of sodium arachidonate (10(-4) M) to organ culture medium caused an approximate two- to fivefold increase (P less than 0.02) in mucin release compared with control and an increase in the secretory component of total glycoprotein synthesis from 37.5% in control explants to 75.2% (P less than 0.01). The stimulatory effect of arachidonate on mucin secretion was blocked by indomethacin. We incubated explants for 1 h with [14C]arachidonate and s...