The Department of Pharmacology Proudly Present the Seminar Series: Frontiers in Pharmacology
“Beta-adrenergic receptor resensitization – an unsuspecting player in pathology”
Of the estimated 200 G-protein coupled receptors in the heart, beta adrenergic receptors (βARs) are considered one of the most powerful regulators of cardiac function and the most common therapeutic agents for management of heart failure. βAR down-regulation and desensitization are hallmarks of heart failure. Agonist stimulation leads to βAR desensitization by phosphorylation through G-protein coupled receptor kinases (GRKs) and protein kinase A (PKA). Phosphorylated βARs are internalized into endosomes which is facilitated by phosphatidylinositol 3-kinase gamma (PI3Kγ). These phosphorylated βARs undergo resensitization by dephosphorylation mediated by Protein Phosphatase 2A (PP2A) in the endosomes. Studies from our lab using cell systems have shown that resensitization is not a passive homeostatic process but a PI3Kγ-regulated mechanism wherein alterations of this process can have significant effects on the outcomes of beta-receptor function. βAR desensitization mechanisms are considered to underlie heart failure pathology while very little is known about role of resensitization. Our studies have been focused on understanding the role of resensitization and its contribution to pathology which will be discussed in the presentation.
Sathyamangla Prasad, PhD FAHA
Dept. of Molecular Cardiology,
Lerner Research Institute
Cleveland Clinic, Cleveland, Ohio
Tuesday, Aug. 16, 2016
(Rm. # 1005)
Light refreshments will be served.
Host : Kevin Xiang