Arrestins in the Cardiovascular System - Progress in Molecular Biology and Translational Science - page 287

CHAPTER TWELVE

Arrestins in the Cardiovascular
System

Anastasios Lymperopoulos, Ashley Bathgate
Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale,
Florida, USA

Contents
1. Introduction 298

2. Cardiovascular Adrenergic Receptors and barrs 299

2.1 a 1 -Adrenergic receptors 299

2.2 a 2 -Adrenergic receptors 300

2.3 b-Adrenergic receptors 305

3. Cardiovascular Angiotensin II Receptors and barrs 309

3.1 Angiotensin II type 1 receptors 309

3.2 Angiotensin II type 2 receptors 314

4. Other Cardiovascular GPCRs and barrs 315

4.1 Endothelin receptors 315

4.2 Vasopressin receptors 316

4.3 Niacin receptor (GPR109A) 317

4.4 P2Y Receptors 318

4.5 Protease-activated receptors 320

5. Cardiovascular Non-GPCRs and barrs 320

6. Biased Agonism/Antagonism of Cardiovascular GPCR Ligands 322

7. Perspectives and Future Directions 326

8. Conclusions 327

References 328

Abstract
Of the four mammalian arrestins, only the b-arrestins (barrs; Arrestin2 and -3) are
expressed throughout the cardiovascular system, where they regulate, as either desen-
sitizers/internalizers or signal transducers, several G-protein-coupled receptors (GPCRs)
critical for cardiovascular homeostasis. The cardiovascular roles of barrs have been delin-
eated at an accelerated pace via a variety of techniques and tools, such as knockout
mice, siRNA knockdown, artificial or naturally occurring polymorphic GPCRs, and avail-
ability of new barr “ biased ” GPCR ligands. This chapter summarizes the current knowl-
edge of cardiovascular arrestin physiology and pharmacology, addressing the individual
cardiovascular receptors affected by barrs in vivo, as well as the individual cell types,