Pharmacological and Molecular Studies for the Regulation of beta_1-Adrenergic Receptors that Reveals Activation and Inactivation

摘要

The physiological regulation of beta_1-Adrenergic Receptors (beta_1AR), 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 have mutated important binding sites of beta_1AR based on molecular modeling that differ in signal length, degree of agonist dependent and independent internalization, and constitutive activation of receptors. The study also clarify the mutation of important site of beta_1AR can undergo signaling through G protein independent pathway whether receptor is functionally inactive.