Endoplasmic reticulum proliferates without an increase in cytochrome P-450 in hepatocytes of mice treated with phenobarbital and cobalt chloride.
To determine whether endoplasmic reticulum (ER) proliferation in hepatocytes after phenobarbital (PB) administration relates closely to cytochrome P-450 (P-450) increase, we have measured the amount of total P-450 per unit cytoplasmic volume (P-450 content) by microphotometry and estimated the area of ER per unit cytoplasmic volume (ER area) by morphometry in periportal, midzonal, and perivenular hepatocytes of mice injected daily with PB (100 mg/kg), or with PB (100 mg/kg) plus cobalt chloride (50 mg/kg) for three days. After injection of PB, the P-450 content and ER area increased in hepatocytes of the three sublobular zones. In mice treated with PB plus cobalt chloride, however, the ER area increased, but the P-450 content decreased or remained unchanged in hepatocytes of the three zones. We conclude that cobalt chloride inhibits the increase in total P-450 but has no effect on the proliferation of ER of hepatocytes in mice treated with PB, indicating a dissociation of ER proliferation and P-450 increase after administration of PB.
Amatsu
T
T
Department of Anatomy, Kansai Medical University, Osaka, Japan.
Watanabe
J
J
Asaka
Y
Y
Kanamura
S
S
D000818:Animals; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry
D010743:Phospholipids; D003035:Cobalt; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C018021:cobaltous chloride; D010634:Phenobarbital