1-2-dioleoyloxy-3-(trimethylammonium)propane and oleylamide

We investigated the effects of oleamide, a fatty acid amide isolated from the cerebrospinal fluid of sleep-deprived cats, on serotonin receptor-mediated signaling in cultured mammalian cells. Oleamide demonstrated opposing effects on 5-HT2A and 5-HT7 receptors, in rat pituitary cells and transfected HeLa cells, respectively. Oleamide caused a potentiation of 5-HT-elicited inositol phosphate formation mediated by the 5-HT2A receptor, but inhibited the effects of 5-HT on cAMP production mediated by the 5-HT7 receptor. In addition, oleamide alone caused a significant increase in cAMP accumulation that was dependent on the presence of the 5-HT7 receptor, but was not blocked by clozapine. These results demonstrate that oleamide can have diverse effects on 5-HT-mediated signal transduction at different subtypes of mammalian 5-HT receptors. Additionally, our data suggest that oleamide may act at an allosteric site on the 5-HT7 receptor and can elicit functional responses via activation of this site.

Topics: Animals; Cats; Cerebrosides; Clozapine; Cyclic AMP; Fatty Acids, Monounsaturated; Fluorescent Dyes; HeLa Cells; Humans; Inositol Phosphates; Oleic Acids; Pituitary Gland; Pituitary Neoplasms; Quaternary Ammonium Compounds; Rats; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Recombinant Proteins; Serotonin; Signal Transduction; Sleep Deprivation; Transfection