Tags

Type your tag names separated by a space and hit enter

The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver.
Pharmacol Res Commun. 1985 Jun; 17(6):513-24.PR

Abstract

The study is concerned with the effects of cimetidine (C), ranitidine (R) and oxmetidine (O) on rat liver cells, in order to compare the effects of increasing amounts of the drugs on various metabolic pathways and on hepatocyte morphology, and their relationship with the drug structure, namely the presence of an imidazole or furan ring. In vitro, an inhibition of ethylmorphine N-demethylase (E-DM) (60%) and of aniline hydroxylase (A-OH) (20%) was observed when either C or R were added at a concentration higher than 0.5 mM to microsomes from untreated rats. Microsomes from phenobarbital or 3-methylcholanthrene-pretreated animals showed a 30 to 40% inhibition of E-DM (mixed type inhibition). In vivo, administration of a single dose (475 microM/kg) of R was followed by an inhibition of E-DM activity, significantly less pronounced (p less than 0.05) than following an equimolar amount of C, whereas O did not alter the enzymatic activity. The amount of cytochrome P-450 and the activities of NADPH cytochrome c reductase and of A-OH were substantially unaffected. No changes of smooth endoplasmic reticulum or of other liver cell organelles were observed by electron microscopy. These findings demonstrate that both in vivo and in vitro E-DM appears as the more sensitive among the pathways considered. Moreover the data support the view that the mere presence of the imidazole ring does not account for the inhibitory effect of H2 antagonists.

Authors

Mosca P
No affiliation info available
Freddara U
No affiliation info available
Lorenzini I
No affiliation info available
Venturini C
No affiliation info available
Jezequel AM
No affiliation info available
Orlandi F
No affiliation info available

MeSH

AnimalsCimetidineHistamine H2 AntagonistsImidazolesIn Vitro TechniquesLiverMaleMicrosomes, LiverMixed Function OxygenasesRanitidineRatsRats, Inbred Strains

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2862646

Citation

Mosca, P, et al. "The Effects of H2 Receptor Antagonists On Hepatic Microsomal Drug Metabolism and Fine Morphology of Rat Liver." Pharmacological Research Communications, vol. 17, no. 6, 1985, pp. 513-24.
Mosca P, Freddara U, Lorenzini I, et al. The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver. Pharmacol Res Commun. 1985;17(6):513-24.
Mosca, P., Freddara, U., Lorenzini, I., Venturini, C., Jezequel, A. M., & Orlandi, F. (1985). The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver. Pharmacological Research Communications, 17(6), 513-24.
Mosca P, et al. The Effects of H2 Receptor Antagonists On Hepatic Microsomal Drug Metabolism and Fine Morphology of Rat Liver. Pharmacol Res Commun. 1985;17(6):513-24. PubMed PMID: 2862646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver. AU - Mosca,P, AU - Freddara,U, AU - Lorenzini,I, AU - Venturini,C, AU - Jezequel,A M, AU - Orlandi,F, PY - 1985/6/1/pubmed PY - 1985/6/1/medline PY - 1985/6/1/entrez SP - 513 EP - 24 JF - Pharmacological research communications JO - Pharmacol Res Commun VL - 17 IS - 6 N2 - The study is concerned with the effects of cimetidine (C), ranitidine (R) and oxmetidine (O) on rat liver cells, in order to compare the effects of increasing amounts of the drugs on various metabolic pathways and on hepatocyte morphology, and their relationship with the drug structure, namely the presence of an imidazole or furan ring. In vitro, an inhibition of ethylmorphine N-demethylase (E-DM) (60%) and of aniline hydroxylase (A-OH) (20%) was observed when either C or R were added at a concentration higher than 0.5 mM to microsomes from untreated rats. Microsomes from phenobarbital or 3-methylcholanthrene-pretreated animals showed a 30 to 40% inhibition of E-DM (mixed type inhibition). In vivo, administration of a single dose (475 microM/kg) of R was followed by an inhibition of E-DM activity, significantly less pronounced (p less than 0.05) than following an equimolar amount of C, whereas O did not alter the enzymatic activity. The amount of cytochrome P-450 and the activities of NADPH cytochrome c reductase and of A-OH were substantially unaffected. No changes of smooth endoplasmic reticulum or of other liver cell organelles were observed by electron microscopy. These findings demonstrate that both in vivo and in vitro E-DM appears as the more sensitive among the pathways considered. Moreover the data support the view that the mere presence of the imidazole ring does not account for the inhibitory effect of H2 antagonists. SN - 0031-6989 UR - https://www.unboundmedicine.com/medline/citation/2862646/The_effects_of_H2_receptor_antagonists_on_hepatic_microsomal_drug_metabolism_and_fine_morphology_of_rat_liver_ DB - PRIME DP - Unbound Medicine ER -