Metabolism of N-acylated-dopamine

PLoS One. 2014 Jan 22;9(1):e85259. doi: 10.1371/journal.pone.0085259. eCollection 2014.

Abstract

N-oleoyl-dopamine (OLDA) is a novel lipid derivative of dopamine. Its biological action includes the interaction with dopamine and the transient receptor potential vanilloid (TRPV1) receptors. It seems to be synthesized in a dopamine-like manner, but there has been no information on its degradation. The aim of the study was, therefore, to determine whether OLDA metabolism proceeds the way dopamine proper does. We addressed the issue by examining the occurrence of O-methylation of exogenously supplemented OLDA via catechol-O-methyltransferase (COMT) under in vitro, ex vivo, and in vivo conditions using rat brain tissue. The results show that OLDA was methylated by COMT in all conditions studied, yielding the O-methylated derivative. The methylation was reversed by tolcapone, a potent COMT inhibitor, in a dose-dependent manner. We conclude that OLDA enters the metabolic pathway of dopamine. Methylation of OLDA may enhance its bioactive properties, such as the ability to interact with TRPV1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Animals
  • Benzophenones / pharmacology
  • Binding, Competitive
  • Brain / metabolism*
  • Catechol O-Methyltransferase / metabolism*
  • Catechol O-Methyltransferase Inhibitors
  • Chromatography, High Pressure Liquid
  • Dopamine / analogs & derivatives*
  • Dopamine / metabolism
  • Male
  • Methylation / drug effects
  • Nitrophenols / pharmacology
  • Rats
  • Rats, Wistar
  • Spectrophotometry
  • TRPV Cation Channels / metabolism
  • Tandem Mass Spectrometry
  • Tolcapone

Substances

  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Nitrophenols
  • TRPV Cation Channels
  • Tolcapone
  • Catechol O-Methyltransferase
  • N-oleoyldopamine
  • Dopamine

Grants and funding

This research was funded by the statutory budget of the Polish Academy of Sciences Medical Research Center in Warsaw. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.