The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties

Marcelis Van Der Stelt, Anna Maria Paoletti, Mauro Maccarrone, Willem F. Nieuwenhuizen, Giacinto Bagetta, Gerrit A. Veldink, Alessandro Finazzi Agrò, Johannes F G Vliegenthart

Research output: Contribution to journalArticle

Abstract

As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH2 influences their binding abilities to the CB-1 receptor and whether it alters their reactivity towards a fatty acid amide hydrolase (FAAH) from rat brain. Neither the fatty acid amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [3H]CP 55.940 from the CB-1 receptor (K(i) >1 μM). Hydroxylation of ODNHEtOH resulted in a strong reduction of the maximum rate of hydrolysis by a FAAH, but the affinity of FAAH for the substrate remained of the same order of magnitude. Hydroxylation of ODNH2 led to a decrease in the affinity of FAAH for the substrate, but its maximum rate of conversion was unaffected. Furthermore, hydroxylation of ODNHEtOH enhanced its capacity to inhibit competitively the hydrolysis of anandamide. The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on cellular signal transduction.

Original languageEnglish
Pages (from-to)313-316
Number of pages4
JournalFEBS Letters
Volume415
Issue number3
DOIs
Publication statusPublished - Oct 6 1997

Fingerprint

Hydroxylation
Amides
Hydrolysis
Fatty Acids
Derivatives
Signal transduction
Cannabinoids
Substrates
Signal Transduction
Brain
fatty-acid amide hydrolase
anandamide

Keywords

  • Anandamide
  • Cannabinoid receptor
  • Fatty acid amide hydrolase
  • Lipoxygenase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Van Der Stelt, M., Paoletti, A. M., Maccarrone, M., Nieuwenhuizen, W. F., Bagetta, G., Veldink, G. A., ... Vliegenthart, J. F. G. (1997). The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties. FEBS Letters, 415(3), 313-316. https://doi.org/10.1016/S0014-5793(97)01148-4

The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties. / Van Der Stelt, Marcelis; Paoletti, Anna Maria; Maccarrone, Mauro; Nieuwenhuizen, Willem F.; Bagetta, Giacinto; Veldink, Gerrit A.; Finazzi Agrò, Alessandro; Vliegenthart, Johannes F G.

In: FEBS Letters, Vol. 415, No. 3, 06.10.1997, p. 313-316.

Research output: Contribution to journalArticle

Van Der Stelt, M, Paoletti, AM, Maccarrone, M, Nieuwenhuizen, WF, Bagetta, G, Veldink, GA, Finazzi Agrò, A & Vliegenthart, JFG 1997, 'The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties', FEBS Letters, vol. 415, no. 3, pp. 313-316. https://doi.org/10.1016/S0014-5793(97)01148-4
Van Der Stelt M, Paoletti AM, Maccarrone M, Nieuwenhuizen WF, Bagetta G, Veldink GA et al. The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties. FEBS Letters. 1997 Oct 6;415(3):313-316. https://doi.org/10.1016/S0014-5793(97)01148-4
Van Der Stelt, Marcelis ; Paoletti, Anna Maria ; Maccarrone, Mauro ; Nieuwenhuizen, Willem F. ; Bagetta, Giacinto ; Veldink, Gerrit A. ; Finazzi Agrò, Alessandro ; Vliegenthart, Johannes F G. / The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties. In: FEBS Letters. 1997 ; Vol. 415, No. 3. pp. 313-316.
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