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 studied prostaglandin and thromboxane products in medium by high-performance liquid chromatography. The only conversion product identified was 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin. Release of gallbladder mucin is significantly inhibited by indomethacin and increased by arachidonate. Mucin secretion may be regulated in part by endogenous levels of prostacyclin, the major cyclooxygenase product in prairie dog gallbladder epithelium.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009077:Mucins / Q000096:biosynthesis / Q000378:metabolism*; D009924:Organ Culture Techniques; D012377:Rodentia
D001095:Arachidonic Acids; D006023:Glycoproteins; D009077:Mucins; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin