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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cats
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Cerebrosides / pharmacology
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Clozapine / pharmacology
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Cyclic AMP / metabolism
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Fatty Acids, Monounsaturated
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Fluorescent Dyes
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HeLa Cells
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Humans
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Inositol Phosphates / metabolism
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Oleic Acids / cerebrospinal fluid
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Oleic Acids / isolation & purification
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Oleic Acids / pharmacology*
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Pituitary Gland
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Pituitary Neoplasms
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Quaternary Ammonium Compounds
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Rats
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin / drug effects
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Receptors, Serotonin / physiology*
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Serotonin / pharmacology
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Serotonin / physiology*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Sleep Deprivation / physiology
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Transfection
Substances
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Cerebrosides
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Fatty Acids, Monounsaturated
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Fluorescent Dyes
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Inositol Phosphates
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Oleic Acids
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Quaternary Ammonium Compounds
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin
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Recombinant Proteins
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serotonin 7 receptor
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Serotonin
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oleylamide
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Cyclic AMP
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Clozapine
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1,2-dioleoyloxy-3-(trimethylammonium)propane