Effect of amphetamine on the hepatic endoplasmic reticulum of the pregnant rat.
Search for the elucidation of the mode of action of amphetamines has revealed that this drug brought about changes in the activity of some enzymes bound to the hepatic endoplasmic reticulum of the pregnant and non-pregnant rat. Amphetamine administration caused loss of appetite and changes in enzyme activity due to starvation, however, its effects were assessed applying pair-feeding conditions. Drug-metabolizing activity was increased by amphetamine as measured by coumarin 3-hydroxylase and aminopyrine N-demethylase in both pregnant and non-pregnant animals; aniline hydroxylase was elevated only in pregnant rats. These changes were associated with the enhanced synthesis of microsomal phospholipids as indicated by the increased activity of [14C-Me]S-adenosyl-L-methionine : microsomal phospholipid methyl transferase, de novo synthesis and levels of microsomal phospholipids. These effects were mainly manifest in phosphatidylethanolamine and phosphatidylcholine fractions. Glucose-6-phosphatase activity remained unaltered by amphetamine. Pregnancy alone brought about a reduction of all these microsomal parameters. The rise of hepatic drug metabolism following the administration of amphetamine indicated a compensatory mechanism by means of stimulating enzyme induction processes.
D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology; D013997:Time Factors
D003517:Cyclopentanes; D004140:Dinitrophenols; D010743:Phospholipids; D012436:S-Adenosylmethionine; D006899:Mixed Function Oxygenases; D013974:Thyroxine; D003913:Dextroamphetamine