Competitive inhibition of coumarin 7-hydroxylation by pilocarpine and its interaction with mouse CYP 2A5 and human CYP 2A6

British Journal of Pharmacology
T KinonenR O Juvonen

Abstract

1. We have shown earlier that pilocarpine strongly inhibits mouse and human liver coumarin 7-hydroxylase activity of CYP 2A and pentoxyresorufin O-deethylase activity of CYP 2B in vitro. Since pilocarpine, like coumarin, contains a lactone structure we have studied in more detail its inhibitory potency on mouse and human liver coumarin 7-hydroxylation. 2. Pilocarpine was a competitive inhibitor of coumarin 7-hydroxylase in vitro both in mouse and human liver microsomes although it was not a substrate for CYP 2A5. Ki values were similar, 0.52 +/- 0.22 microM in mice and 1.21 +/- 0.51 microM in human liver microsomes. 3. Pilocarpine induced a type II difference spectrum in mouse, human and recombinant CYP 2A5 yeast cell microsomes, with Ka values of 3.7 +/- 1.6, 1.6 +/- 1.1 and 1.5 +/- 0.1 microM, respectively. 4. Increase in pH of the incubation medium from pH 6 to 7.5 increased the potency of inhibition of coumarin 7-hydroxylation by pilocarpine. 5. Superimposition of pilocarpine and coumarin in such a way that their carbonyls, ring oxygens and the H-7' of coumarin and N-3 of pilocarpine overlap yielded a common molecular volume of 82%. 6. The results indicate that pilocarpine is a competitive inhibitor and has a high affinity ...Continue Reading

References

Apr 1, 1978·Analytical Biochemistry·A Aitio
Nov 1, 1991·Molecular Pharmacology·C H YunF P Guengerich
Jun 5, 1987·Journal of Molecular Biology·T L PoulosA J Howard
Oct 1, 1985·Analytical Biochemistry·P K SmithD C Klenk
Jan 1, 1985·British Journal of Clinical Pharmacology·O PelkonenJ T Ahokas
Oct 1, 1972·Japanese Journal of Pharmacology·A TsujimotoS Kojima
Jan 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G G Gibson, P P Tamburini
Feb 1, 1995·British Journal of Pharmacology·T KimonenM Pasanen

❮ Previous
Next ❯

Citations

Jul 12, 2008·Archives of Toxicology·Olavi PelkonenHannu Raunio
Oct 31, 2002·Advanced Drug Delivery Reviews·Chun XuRachel F Tyndale
Nov 14, 1997·Toxicology·M PasanenA Rautio
Apr 27, 2000·Toxicology·O PelkonenM Pasanen
Mar 26, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D F V LewisP S Goldfarb
Oct 18, 2011·Archives of Toxicology·Adolfo Sierra-SantoyoMichael F Hughes
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
May 15, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A M BelliardR Farinotti
Aug 13, 1999·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·D F Lewis
Dec 2, 2017·Journal of Personalized Medicine·Julie-Anne Tanner, Rachel F Tyndale
Sep 15, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Marycarmen Cruz-HurtadoAdolfo Sierra-Santoyo
Nov 24, 2018·Chemical Biology & Drug Design·Mira AhinkoOlli T Pentikäinen
Jul 6, 2016·Wiener medizinische Wochenschrift·Miloš D Pavlović
Dec 21, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Takuro EndoYasunori Momose
Nov 5, 2011·The FEBS Journal·Natasha M DeVoreEmily E Scott
Mar 12, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Risto O JuvonenOlli T Pentikäinen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.