Primary fatty acid amides constitute an important new class of hormones. Oleamide (C18H35NO), for example has been found to be a potent neuro- modulator of serotonin-5-HT binding, to inhibit gap junction communication in glial cells, and to cause physiological sleep upon injection. Oleamide and several other primary fatty acid amides are implicated as a crucial hormone system which may act to modulate the effects of the primary peptide, catecholamine, and serotonin hormones. The link to affective disorders via serotonin and sleep induction is particularly exciting. Mental disorders such as depression, bipolar disorder, and schizophrenia are poorly understood, and there are no clinical markers. An estimated one American in six has some form of affective disorder, making the need for better treatment and diagnosis options urgent. Because this field is still emergent, little is actually known about their biosynthesis, metabolism, transport, and mode of action, particularly for amides other than oleamide. Current findings may constitute trace evidence of a wide array of compounds. These compounds are potent, easily hydrolyzed, and lipophilic, making basal levels, especially in extracellular fluid, quite low (nanomolar or below). For this field to continue to progress, it is crucial that presence, diversity, and basal levels of these compounds be established. The proposed work, if successful, will provide such a characterization.
Its specific aims are to: Assay selected tissue samples for saturated and unsaturated primary fatty acid amides using gas chromatography with mass spectrometric detection to provide information at the upper concentration range.
This aim will provide timely information for an emerging field as well as a standard method. Develop a screening method with high throughput and sensitivity based on selective fluorescence derivatization and on-line sample preparation. Previous samples will be re-assayed to determine the lower concentration range, and to determine whether there are indeed numerous members of this hormone family.
