Oleamide‐induced Modulation of 5‐Hydroxytryptamine Receptor‐mediated Signalinga

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Abstract
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.