Aflatoxin B1 is an inhibitor of cyclic nucleotide phosphodiesterase activity

Paola Bonsi, Gabriella Augusti-Tocco, Maura Palmery, Mauro Giorgi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aflatoxin B1 (AFB1) action on cyclic nucleotide phosphodiesterase (PDE) activity has been tested on tissue extracts of various organs. In the presence of 100 μM AFB1 a significant inhibition of cAMP and cGMP hydrolytic activity is observed in all tested tissue extracts. However, cGMP hydrolytic activity appears more sensitive to AFB1 inhibition than cAMP hydrolytic activity and a considerably higher inhibition is observed in lung and spleen, than in liver, brain, kidney, and heart. When cGMP is used as substrate, the inhibitory response reaches 72% in lung and spleen extracts. We have also tested AFB1 effects on lung and liver PDE activity peaks separated by DEAE-cellulose chromatography. These data confirm the poor sensitivity to the toxin of all PDE activities present in liver, while the lung peak (where PDE V in present) shows a higher sensitivity to AFB1. In order to establish whether PDE V is in fact more sensitive to AFB1, we have used mouse neuroblastoma cells, in which cGMP hydrolytic activity has been shown to be due to PDE V only. In this case, the calculated IC50 is 24 μM and Dixon plot analysis shows a competitive inhibitory effect with a Ki of 16.7 μM. We have also used aflatoxin B2 and M2, and they proved to be much less effective than AFB1: AFB2 inhibits PDE V with an IC50 of 117 μM, while AFM2 does not show any effect. These results provide the first evidence of a competitive inhibition of AFB1 on an enzymatic activity and suggest that an alteration of cellular cyclic nucleotide levels may play a role in the mechanism of aflatoxin action. All rights reserved. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)615-619
Number of pages5
JournalGeneral Pharmacology
Volume32
Issue number5
DOIs
Publication statusPublished - May 1999

Fingerprint

Aflatoxin B1
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Type 5 Cyclic Nucleotide Phosphodiesterases
Lung
Tissue Extracts
Inhibitory Concentration 50
Liver
Spleen
DEAE-Cellulose Chromatography
Aflatoxins
Neuroblastoma
Kidney
Brain

Keywords

  • Aflatoxin B
  • High affinity cyclic nucleotide phosphodiesterase
  • PDE V isoform

ASJC Scopus subject areas

  • Pharmacology

Cite this

Aflatoxin B1 is an inhibitor of cyclic nucleotide phosphodiesterase activity. / Bonsi, Paola; Augusti-Tocco, Gabriella; Palmery, Maura; Giorgi, Mauro.

In: General Pharmacology, Vol. 32, No. 5, 05.1999, p. 615-619.

Research output: Contribution to journalArticle

Bonsi, Paola ; Augusti-Tocco, Gabriella ; Palmery, Maura ; Giorgi, Mauro. / Aflatoxin B1 is an inhibitor of cyclic nucleotide phosphodiesterase activity. In: General Pharmacology. 1999 ; Vol. 32, No. 5. pp. 615-619.
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