Effect of neurotransmitters on NADPH-cytochrome P450 reductase in vitro activity.
Article Details
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Gervasini G, Martinez C, Benitez J, Agundez JA
Effect of neurotransmitters on NADPH-cytochrome P450 reductase in vitro activity.
Drug Metab Lett. 2007 Aug;1(3):172-5.
- PubMed ID
- 19356039 [ View in PubMed]
- Abstract
Three neurotransmitters, namely adrenaline, serotonin and tryptamine inhibit the in vitro activity of several cytochrome P450 (CYP) isozymes (CYP1A2, CYP2C9, CYP2D6 and CYP3A). In order to test whether this effect is related to inhibition of the CYP-coupled NADPH reductase activity, we assayed the potential inhibitory effect of these neurotransmitters and their main metabolites on the NADPH reductase activity. Of the five compounds analyzed: tryptamine, tryptophol, serotonin, 5-hydroxytryptamine and adrenaline, only adrenaline significantly decreased NADPH reductase activity at the fixed concentration of 500 microM. However, the effect became negligible when adrenaline concentration was decreased to 100 microM: whereas a high inhibitory effect was observed in CYP2D6, CYP2C9 and CYP3A4 enzyme activities, the NADPH reductase activity remains unchanged. This study indicates that the effect of these endogenous neurotransmitters on CYP enzymes is not related to changes in the reductase activity. In the light of these findings further studies on the inhibitory effect of these neurotransmitters on CYP enzymes can be designed ruling out the modulation of the coupled NADPH reductase activity as a confounding factor.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Epinephrine Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Epinephrine Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails