Effects of 16,16-dimethyl prostaglandin E2 on biliary mucous glycoprotein and gallstone formation in guinea pigs.
This study was performed to determine the effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on mucous glycoprotein secretion by the guinea pig gallbladder. The prostaglandin was given intraperitoneally for 4 weeks at daily doses of 0 (controls), 10, 20, or 30 micrograms/kg body weight (n = 18 at each dose). These 72 animals were fed normal chow. A 5th group of 18 animals received chow containing 1% cholesterol and 0.5% cholic acid, and no dmPGE2. There were statistically significant increases in the concentrations in gallbladder bile of mucous glycoprotein in the animals fed cholesterol and those treated with dmPGE2, as compared with the controls. Moreover, the animals treated with dmPGE2 formed black-pigmented gallstones, the incidence being dose-dependent, whereas all animals fed a cholesterol-rich diet formed amorphous yellow-brown gallstones. Even though these two types of gallstones appeared different on macroscopic examination, both consisted primarily of calcium phosphate and calcium bilirubinate. These results suggest that exogenous prostaglandin E2 increases concentrations of mucous glycoprotein in the gallbladder bile, resulting in gallstone formation by a mechanism in part similar to the one whereby cholesterol loading promotes gallstone formation in this model.
Sasaki
H
H
First Dept. of Internal Medicine, Hiroshima University School of Medicine, Japan.
Tazuma
S
S
Kajiyama
G
G
D015064:16,16-Dimethylprostaglandin E2 / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000187:drug effects*; D002769:Cholelithiasis / Q000139:chemically induced* / Q000737:chemistry; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006023:Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male
D002791:Cholesterol, Dietary; D006023:Glycoproteins; C047874:gastric mucus glycoproteins; D015064:16,16-Dimethylprostaglandin E2