Pharmacology & Therapeutics of Constitutively Active Receptors :

Content: Front Cover
 Pharmacology & Therapeutics of Constitutively Active Receptors
 Copyright
 Contents
 Preface
 Contributors
 Chapter One: Constitutively Active Rhodopsin and Retinal Disease
 1. Introduction
 2. Rhodopsin Activity
 2.1. Physiology of rhodopsin activity
 2.2. Molecular switches that lock rhodopsin in an inactive state
 3. Constitutive Activity in Rhodopsin that Causes Disease
 3.1. Leber congenital amaurosis and vitamin A deficiency
 3.1.1. Opsin: Active apoprotein
 3.2. Congenital night blindness
 3.2.1. G90D: Active dark state
 3.2.2. T94I, A292E, and A295V: Active dark state. 3.3. Retinitis pigmentosa3.3.1. S186W and D190N: Thermal activation
 3.3.2. G90V: Active dark state and thermal activation
 3.3.3. K296E: Active apoprotein and stable arrestin interactions
 4. How Constitutive Activity Can Cause Different Phenotypes
 4.1. Different levels of activity as an underlying cause of different phenotypes
 4.2. Do all constitutively active mutants adopt the same active-state conformation?
 5. Conclusion
 Conflict of Interest
 Acknowledgments
 References
 Chapter Two: Constitutive Activity in Gonadotropin Receptors
 1. Introduction. 2. Naturally Occurring CAMs of the Gonadotropin Receptors2.1. CAMs of the human LHCGR
 2.2. CAMs of the human FSHR
 3. Experimental Models of Gonadotropin Receptor CAMs
 3.1. LHCGR CAMs and LH/hCG overexpressing mice
 3.2. FSHR CAMs and FSHR overexpressing mice
 4. Molecular Basis of Constitutive Activity in Gonadotropin Receptors
 4.1. Mechanism of ligand-induced activation in gonadotropin receptors
 4.2. Mechanisms leading to constitutive activity of gonadotropin receptors
 5. Design of New Molecules for Controlling the Activity of Constitutively Active Gonadotropin Receptors
 6. Conclusion. Conflict of InterestAcknowledgments
 References
 Chapter Three: Constitutive Activities in the Thyrotropin Receptor: Regulation and Significance
 1. Introduction
 2. Constitutive Activity in the Thyrotropin Receptor
 2.1. Properties related to Gs-mediated basal signaling activity
 2.1.1. Structural determinants involved in regulation of basal signaling activity
 2.1.2. Physiological aspects of basal signaling
 2.2. Modulation of constitutive signaling activity
 2.2.1. Constitutive signaling activity induced by mutations
 2.2.2. Silencing of constitutive activity. 2.2.2.1. Constitutive inactivation by mutations2.2.2.2. Small-molecule ligands with inverse agonistic properties
 2.2.2.3. Antibodies with inverse agonistic properties
 3. Conclusion
 Conflict of Interest
 Acknowledgments
 References
 Chapter Four: Constitutive Activity in Cannabinoid Receptors
 1. Introduction
 2. Challenges in Proving Constitutive Receptor Activity
 2.1. Demonstrating constitutive receptor activity requires the use of agonist, inverse agonist, and neutral antagonist
 2.2. Constitutive active receptor versus constitutive agonist tone.