THE EFFECT OF HYDROXYLATION OF LINOLEOYL AMIDES ON THEIR CANNABINOMIMETIC PROPERTIES

As yet, the physiological significance of hydroxylation of anandamide and linoleoyl amides is unknown, Therefore, we investigated whether hy droxylation of ODNHEtOH and ODNH2 influences their binding abilities t o the CB-1 receptor and whether it alters their reactivity towards a f atty acid amide hydrolase (FAAH) from rat brain, Neither the fatty aci d amides nor their hydroxylated derivatives were able to displace the potent cannabinoid [H-3]CP 55.940 from the CB-I receptor (K-i>1 mu M), Hydroxylation of ODNHEtOH resulted in a strong reduction of the maxim um rate of hydrolysis by a FAAH, but the affinity of FAAH for the subs trate 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 hydroly sis of anandamide, The resulting prolonged lifetime of anandamide and other fatty acid amide derivatives may have a considerable impact on c ellular signal transduction. (C) 1997 Federation of European Biochemic al Societies.