Allyn Howlett PhD

Dr. Howlett's laboratory investigates the mechanisms by which cannabinoid drugs and endocannabinoid compounds stimulate the CB1 cannabinoid receptor to select intracellular signal transduction pathways. Cultured neuronal cells are used to define the types of G proteins that interact with the CB1 receptor, and investigate the necessary receptor domains. Phosphorylation of the receptor is an important means to direct signaling through specific G proteins or other signaling proteins such as beta-arrestin, G protein associated sorting protein (GASP) and Cannabinoid Receptor Interacting Protein (CRIP). These studies will assess the potential for drugs to promote partnering with different G proteins and accessory proteins and thereby direct the selection of signal transduction pathways (e.g., via adenylyl cyclase inhibition, MAPK activation, Ca2+ regulation, and NO production). The importance to drug discovery is the promotion of therapeutically beneficial actions analgesia with diminished untoward side effects sedation, cognitive dysfunction.