Fatty acid amides (FAAs) represent an emerging class of lipid messengers that influence a variety of behavioral responses including pain sensation, anxiety, sleep, and feeding. Genetic and pharmacological studies have demonstrated that fatty acid amide hydrolase (FAAH), an integral membrane enzyme, is the principal regulator of FAA-based signaling events in vivo. FAAH regulates FAA activity by hydrolyzing these neuroactive signaling lipids to their inactive form, thus functionally terminating FAA signaling. The goals of this research proposal are 1) to understand the molecular and cellular mechanisms by which FAAH degrades FAAs and 2) to determine the biochemical effects of blocking degradation of selective FAAs. These goals will be addressed by studying the roles of FAAH channels in substrate selectivity, hydrolysis, and product release and by applying these in vitro results in designing transgenic mice for biochemical analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA019425-02
Application #
7015058
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2005-01-01
Project End
2006-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
2
Fiscal Year
2006
Total Cost
$23,522
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
McKinney, Michele K; Cravatt, Benjamin F (2006) Structure-based design of a FAAH variant that discriminates between the N-acyl ethanolamine and taurine families of signaling lipids. Biochemistry 45:9016-22
Saghatelian, Alan; McKinney, Michele K; Bandell, Michael et al. (2006) A FAAH-regulated class of N-acyl taurines that activates TRP ion channels. Biochemistry 45:9007-15