Premium
The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties
Author(s) -
van der Stelt Marcelis,
Paoletti Anna Maria,
Maccarrone Mauro,
Nieuwenhuizen Willem F,
Bagetta Giacinto,
Veldink Gerrit A,
Finazzi Agrò Alessandro,
Vliegenthart Johannes F.G
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01148-4
Subject(s) - anandamide , fatty acid amide hydrolase , hydroxylation , chemistry , endocannabinoid system , amidase , amide , cannabinoid , substrate (aquarium) , biochemistry , cannabinoid receptor , stereochemistry , fatty acid , hydrolysis , enzyme , receptor , biology , ecology , agonist
As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown. Therefore, we investigated whether hydroxylation of ODNHEtOH and ODNH 2 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 [ 3 H]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 ODNH 2 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.