AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 5 701-G709, Copyright © 1986 by American Physiological Society
Gallbladder prostaglandins and lysophospholipids as mediators of mucin secretion during cholelithiasis
W. W. LaMorte, J. T. LaMont, W. Hale, M. L. Booker, T. E. Scott and B. Turner
Mucin hypersecretion from the gallbladder epithelium contributes to
cholesterol gallstone formation by accelerating the nucleation of
cholesterol-supersaturated bile. Prostaglandins (PGs) and
lysophosphatidylcholine (LPC) have both been implicated as potential
mediators of mucin hypersecretion, but their roles are unclear. We fed
prairie dogs a lithogenic diet (0.34% cholesterol), and after 1, 2, 4, or 6
wk of cholesterol feeding, we measured glycoprotein and LPC concentrations
in bile and PG synthesis in gallbladder and liver slices.
Hypercholesterolemia and cholesterol supersaturation of bile occurred after
1 wk of cholesterol feeding, but marked crystal formation was delayed until
4 wk, when glycoprotein concentrations became markedly elevated.
Glycoprotein hypersecretion was preceded by increased synthesis of PGF2
alpha (P less than 0.002), PGE2 (P less than 0.001), prostacyclin (P less
than 0.05), and thromboxane (P = 0.07) in the gallbladder after only 2 wk
of cholesterol feeding, but PG synthesis in the liver remained unchanged (P
greater than 0.14). LPC concentrations in gallbladder bile also increased
at 2 wk (P less than 0.02), but LPC in hepatic bile was unchanged (P =
0.35). In organ culture studies, LPC caused a dose-dependent stimulation of
[3H]glycoprotein release from guinea pig gallbladder mucosa that could not
be explained solely by LPC's detergent properties. We conclude that
gallbladder PG synthesis and LPC production are increased at an early stage
of cholesterol gallstone formation in the prairie dog model. These changes
probably play a significant role in gallstone pathogenesis, since they
mediate hypersecretion of gallbladder mucin and thus favor the nucleation
of cholesterol-supersaturated bile.
