The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties

FEBS Letters

Nieuwenhuizen, Willem F²  Vliegenthart, Johannes F.G²  Maccarrone, Mauro¹  van der Stelt, Marcelis²  Bagetta, Giacinto³  Finazzi Agrò, Alessandro¹  Veldink, Gerrit A²  Paoletti, Anna Maria³ 

[1]Department of Experimental Medicine and Biochemical Sciences, University of Rome `Tor Vergata', Via di Tor Vergata 135, I-OO133 Rome, Italy

[2]Bijvoet Center for Biomolecular Research, Department of Bio-Organic Chemistry, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, The Netherlands

[3]`Mondino-Tor Vergata' Center for Experimental Neurobiology, Department of Biology, University of Rome `Tor Vergata', Rome, Italy

关键词: Anandamide;    Lipoxygenase;    Cannabinoid receptor;    Fatty acid amide hydrolase;    BSA;    bovine serum albumin;    CB-1/2;    cannabinoid binding receptor-1/2;    FAAH;    fatty acid amide hydrolase;    12/15-HETE;    12/15-hydroxyeicosatetraenoic acid;    13-HODNHEtOH;    13-(S)-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl ethanolamide;    13-HODNH2;    13-(S)-hydroxy-9Z;    11E-octadeca-9;    11-dienoyl amide;    LCS;    liquid scintillation cocktail;    ODNHEtOH;    9Z;    12Z-octadeca-9;    12-dienoyl ethanolamide;    ODNH2;    9Z;    12Z-octadeca-9;    12-dienoyl amide;    PEI;    polyethylene imine;    PMSF;    phenylmethylsulfonyl fluoride;    RP-HPLC;    reversed phase high performance liquid chromatography;    TLC;    thin layer chromatography;   

DOI  :  10.1016/S0014-5793(97)01148-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown