This is a Research Scientist Award for Dr. Allyn Howlett, who has a B.S. cum laude, in Biochemistry and Ph.D. in Pharmacology and Toxicology. Dr. Howlett is a tenured Professor in the Dept. Pharmacological and Physiological Science at Saint Louis University School of Medicine, a large, technically multidisciplinary department with research interests in cardiovascular, endocrine and neural physiology and pharmacology. Dr. Howlett's research effort is concentrated on the pharmacological, biochemical and cellular regulation of the CB1 cannabinoid receptor. Her intention is to maintain an active research laboratory in which students, fellows and visiting scientists can exchange ideas and share from their areas of expertise. Toward this goal, Dr. Howlett requests the continuation of this RSA in order to allow ample research time to attend to each individual working on the research project and to maintain research collaborations with other scientists. The RSA will also foster continued professional development through research meetings, short courses and communication with other research scientist. Dr. Howlett's research projects have been described in two NIDA-funded R01 grants. """"""""Cannabinoid Receptor Structure-Activity Releationships"""""""" examines the receptor-ligand interaction (cannabinoid, aminoalkylindole, eicosanoid, and other structures) in an effort to define the requirements for high-affinity association and efficacy, such that pharmacologically distinct agonists and antagonist (CB1- or CB2-selective) can be determined or developed. This project involves close collaboration with synthetic, analytical, and computational chemist. """"""""Cannabinoid Receptors in Neuronal Cells and Brain"""""""" addresses the mechanisms through which the receptor signals its response through G proteins, and the mechanisms whereby the cell regulates this activity through modification of the receptor (e.g., phosphorylation, palmitoylation) and regulation of synthesis, cellular localization, and degradation.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Award (K05)
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Human Development Research Subcommittee (NIDA)
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Rapaka, Rao
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Saint Louis University
Schools of Medicine
Saint Louis
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Oddi, Sergio; Dainese, Enrico; Sandiford, Simone et al. (2012) Effects of palmitoylation of Cys(415) in helix 8 of the CB(1) cannabinoid receptor on membrane localization and signalling. Br J Pharmacol 165:2635-51
Gerald, Tonya M; Howlett, Allyn C; Ward, Gregg R et al. (2008) Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex. Psychopharmacology (Berl) 198:497-508
Jones, Jenelle D; Carney, Skyla T; Vrana, Kent E et al. (2008) Cannabinoid receptor-mediated translocation of NO-sensitive guanylyl cyclase and production of cyclic GMP in neuronal cells. Neuropharmacology 54:23-30
Grace, Christy R R; Cowsik, Sudha M; Shim, Joong-Youn et al. (2007) Unique helical conformation of the fourth cytoplasmic loop of the CB1 cannabinoid receptor in a negatively charged environment. J Struct Biol 159:359-68
Ward, Gregg R; Franklin, Steven O; Gerald, Tonya M et al. (2007) Glucocorticoids plus opioids up-regulate genes that influence neuronal function. Cell Mol Neurobiol 27:651-60
McCollum, LaTronya; Howlett, Allyn C; Mukhopadhyay, Somnath (2007) Anandamide-mediated CB1/CB2 cannabinoid receptor--independent nitric oxide production in rabbit aortic endothelial cells. J Pharmacol Exp Ther 321:930-7
Mukhopadhyay, Somnath; Das, Sucharita; Williams, Evelyn A et al. (2006) Lipopolysaccharide and cyclic AMP regulation of CB(2) cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages. J Neuroimmunol 181:82-92
Gerald, Tonya M; Ward, Gregg R; Howlett, Allyn C et al. (2006) CB1 knockout mice display significant changes in striatal opioid peptide and D4 dopamine receptor gene expression. Brain Res 1093:20-4
Shim, Joong-Youn; Howlett, Allyn C (2006) WIN55212-2 docking to the CB1 cannabinoid receptor and multiple pathways for conformational induction. J Chem Inf Model 46:1286-300
Howlett, Allyn C (2005) A short guide to the nomenclature of seven-transmembrane spanning receptors for lipid mediators. Life Sci 77:1522-30

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