Anandamide degradation and N-acylethanolamines level in wild-type and CB1 cannabinoid receptor knockout mice of different ages

Mauro Maccarrone, Marina Attinà, Monica Bari, Antonella Cartoni, Catherine Ledent, Alessandro Finazzi-Agrò

Research output: Contribution to journalArticle

Abstract

CD1 mice lacking the CB1 receptors knockout, KO) were compared with wild-type littermates for their ability to degrade N-arachidonoylethanolamine (anandamide, AEA) through a membrane transporter (AMT) and a fatty acid amide hydrolase (FAAH). The regional distribution and age-dependence of AMT and FAAH activity were investigated. Anandamide membrane transporter and FAAH increased with age in knockout mice, whereas they showed minor changes in wild-type animals. Remarkably, they were higher in all brain areas of 6-month-old knockout versus wild-type mice, and even higher in 12-month-old animals. The molecular mass (≈67 kDa) and isoelectric point (≈7.6) of mouse brain FAAH were determined and the FAAH protein content was shown to parallel the enzyme activity. The kinetic constants of AMT and FAAH in the cortex of wild-type and knockout mice at different ages suggested that different amounts of the same proteins were expressed. The cortex and hippocampus of wild-type and knockout mice contained the following N-acylethanolamines: AEA (8% of total), 2-arachidonoylglycerol (5%), N-oleoylethanolamine (20%), N-palmitoylethanolamine (53%) and N-stearoylethanolamine (14%). These compounds were twice as abundant in the hippocampus as in the cortex. Minor differences were observed in AEA or 2-arachidonoylglycerol content in knockout versus wild-type mice, whereas the other compounds were lower in the hippocampus of knockout versus wild-type animals.

Original languageEnglish
Pages (from-to)339-348
Number of pages10
JournalJournal of Neurochemistry
Volume78
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • Anandamide hydrolase
  • Anandamide transporter
  • CB receptor knockout
  • CD1 mouse
  • Endocannabinoids

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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