Receptors are proteins that nestle in the cell membrane, and which translate external chemical signals such as hormones into a cellular response. Discovering the detailed mechanisms of beta-arrestin action is important because the receptors it "downregulates" number perhaps in the thousands, and control processes throughout the body -- including heart rate; blood pressure; endocrine function; the senses of sight, smell and taste; pain tolerance, and the euphoric high of addictive drugs. Thus, new basic knowledge about the action of beta-arrestin could have implications for development of drugs for a wide array of disorders.
In an article in the October 25, 2002, "Science," Howard Hughes Medical Institute investigator Robert Lefkowitz at Duke University Medical Center and his colleagues reported their studies of the role of beta-arrestin in regulating a "second-messenger" molecule called cyclic AMP (cAMP).
This molecule launches a cascade of metabolic signals into the cell when it is produced by activation of receptors such as the "G-protein-coupled receptors" (GPCRs) studied by Lefkowitz's laboratory. The role of beta-arrestin is to desensitize GPCRs by regulating cAMP levels, to prevent over stimulation of the cell.
"It's been known for a number of years that there are two major mechanisms by which the levels of cyclic AMP are regulated," said Lefkowitz. "One is the rate at which cAMP is synthesized by an enzyme called adenylate cyclase, which in turn is activated by receptors. And the other mechanism is the rate of cyclic AMP degradation, which is carried out by a
Contact: Dennis Meredith