Acute Effect of Amitriptyline, Phenobarbital or Cobaltous Chloride on δ-Aminolevulinic Acid Synthetase, Heme Oxygenase and Microsomal Heme Content and Drug Metabolism in Rat Liver

• Published in: Japanese journal of pharmacology Vol. 50; no. 3; pp. 289 - 293
• Main Authors: HOSHI, Katsuji, SENDA, Naoto, FUJINO, Sumiko
• Format: Journal Article
• Language: English
• Published: Kyoto Japanese Pharmacological Society 01.01.1989
• Subjects: 5-Aminolevulinate Synthetase - antagonists & inhibitors; Amitriptyline - pharmacology; Animals; Biological and medical sciences; Cobalt - pharmacology; Cytochrome b Group - metabolism; Cytochrome P-450 Enzyme System - metabolism; Cytochromes b5; Heme - metabolism; Heme Oxygenase (Decyclizing) - antagonists & inhibitors; In Vitro Techniques; Liver - metabolism; Male; Medical sciences; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Mixed Function Oxygenases - antagonists & inhibitors; Neuropharmacology; Pharmaceutical Preparations - metabolism; Pharmacology. Drug treatments; Phenobarbital - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Inbred Strains; δ-Aminolaevulinate synthase; Enzyme; Psychotropic; Animal; Cytochrome P450; Liver; Haem oxygenase (decyclizing); Antidepressant agent; Cobalt
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)42443-8

Cobaltous chloride (CoCI2) caused very marked decreases of cytochrome P-450, b5 and total heme contents and an increase of heme oxygenase activity. On the contrary, phenobarbital (PB) increased hepatic drug-metabolizing enzymes, but the total heme content remained unchanged. On the other hand, amitriptyline (AMT) caused a marked increase of δ-aminolevulinic acid (δ-ALA) synthetase activity at 12 and 24 hr. In addition, the contents of total heme and cytochrome b5 and the activities of aminopyrine (AM) N-demethylase and aniline (AN) hydroxylase at 24 hr were also increased by AMT, whereas cytochrome P-450 content did not change. This may be explained by the fact that AMT would increase hepatic heme synthesis through the prolonged induction of d-ALA synthetase, but it may not cause an increase in cytochrome P-450 heme because there are increases in the contents of cytochrome b5 and total heme.