AJP - Gastrointestinal and Liver Physiology, Vol 245, Issue 1 92-G98, Copyright © 1983 by American Physiological Society
Arachidonic acid stimulates mucin secretion in prairie dog gallbladder
J. T. LaMont, B. S. Turner, D. DiBenedetto, R. Handin and A. I. Schafer
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.
