William J. Driscoll, Ph.D.
Research Assistant Professor of Anatomy, Physiology and Genetics

University of New Mexico School of Medicine, 1987
 
Research Interests:
Amidated chemical messengers mediate neurochemical and electrophysiological mechanisms essential for normal brain function. Disturbances in these mechanisms are implicated in the pathogenesis of many psychiatric disorders as well as narcolepsy and insomnia. Recently, it was shown that the fatty acid primary amide, oleamide, is a mediator of sleep and may thus contribute to the genesis of sleep disorders. In fact, oleamide accumulates in cerebral spinal fluid during sleep deprivation and, by itself, induces a profound motor quienscence and a sleep-like state upon administration. While the precise functions of oleamide remain to be established, a rapidly growing body of evidence indicates that oleamide represents and exciting new class of signaling molecules whose actions are mediated via receptor-based signal transduction mechanisms. The clinical importance of these actions is reflected in the effectiveness of fatty acid primary amides in the treatment of epilepsy and anxiety.
 
The mechanism by which fatty acid primary amides are synthesized in vivo is presently unknown. Recently, we established that recombinant peptidylglycine-a -amidating monooxygenase (PAM) catalyzes the in vitro formation of oleamide from oleoylglycine, a compound produced endogenously. PAM is the enzyme traditionally known for its role in the bioactivation of many neural and endocrine peptides. In this capacity, PAM is rate limiting and thus may control the production of fatty acid primary amides as well as amidated peptides. Current research efforts are focused on testing the hypothesis that PAM regulates the biosynthesis of fatty acid primary amides in vivo using oleamide as the paradigm. A clear understanding of the biosynthetic pathway for oleamide will allow for the development of specific pharmacologic agents to treat sleep disorders and promote wakefulness.
 
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4301 Jones Bridge Road
Bethesda, Maryland 20814

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