| Affiliation: | (1) The Gladstone Institute of Neurological Disease, The Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA;(2) Departments of Medicine and Molecular and Cellular Pharmacology, University of California, San Francisco, CA 94143, USA |
| Abstract: | Background The physiological regulation of G protein-coupled receptors, through desensitization and internalization, modulates the length of the receptor signal and may influence the development of tolerance and dependence in response to chronic drug treatment. To explore the importance of receptor regulation, we engineered a series of Gi-coupled receptors that differ in signal length, degree of agonist-induced internalization, and ability to induce adenylyl cyclase superactivation. All of these receptors, based on the kappa opioid receptor, were modified to be receptors activated solely by synthetic ligands (RASSLs). This modification allows us to compare receptors that have the same ligands and effectors, but differ only in desensitization and internalization. |
