The Pharmacology of Taste

Description

The Pharmacology of Taste is comprised of contributions by leading scientists from the field of chemosensory research, presented all together in the context of pharmacological principles of receptor function. The chapters cover all levels of scientific inquiry, from molecular and physiological mechanisms underlying taste signaling to its manifestation in overt behavior. The overarching objective of this volume is to inspire the application of concepts and methods of pharmacology to the study of the chemosenses. Preface Contents Why Taste Is Pharmacology 1 Introduction: Paradigms for the Study of Taste 2 The Purview of Pharmacology 2.1 Definitions of Pharmacology 2.2 Definitions of Taste 2.3 The Pharmacology of Taste 3 Essentials of Receptor Occupancy Theory 3.1 The Concentration-Response Function and Its Relationship to Receptor Occupancy 3.1.1 The Operational Model of Agonism 4 Conclusions to be Drawn from Receptor Theory: What Is to be Expected of Taste? 4.1 Characteristics of the Concentration-Response Functions from Cell-Based Assays of Recombinant Tastant Receptors 4.2 Concentration-Dependence of Human Taste 4.2.1 Power Functions for Taste Intensity 4.2.2 The Relationship of Taste Intensity to Taste Thresholds 4.3 Dependent Variables in Human Taste Measurement 5 Concluding Remarks References Taste Receptor Signaling 1 Introduction 2 Organization of the Peripheral Taste System 3 Taste Receptor Cells 4 Type I TRCs 5 Type II TRCs 6 Type III TRCs 7 Broadly Responsive (BR) Taste Cells 8 Transduction Pathways in TRCs 9 GPCR Signaling 10 Bitter Taste Receptors 11 Sweet and Umami Taste Receptors 12 Ionotropic Signaling 13 Salt Transduction 14 Sour Transduction 15 Signaling in BR Cells 16 Conclusions References Encoding Taste: From Receptors to Perception 1 Information Coding in the Peripheral Nervous System 1.1 Exteroreceptors 1.2 Stimulus Intensity 1.3 Stimulus Duration 1.4 Transmitting Sensory Information from the Periphery to the CNS 1.5 Stimulus Modality 1.6 How Do Afferent Fibers Encode Intensity? 1.7 Sensory Afferent Fibers Only Partially Encode Stimulus Duration 1.8 How Do Sensory Afferent Fibers Signal the Location of Stimulation? 2 Information Coding in the Central Nervous System 2.1 Sensory Modalities 3 Sensory Coding in the Gustatory Nervous System: From Taste Buds to Cortex 3.1 How Do Gustatory Membrane Receptors Identify Taste Stimuli? 3.2 Gustatory Stimulus Intensity 3.3 Gustatory Stimulus Duration 3.4 How Do Taste Bud Receptor Cells Discriminate Gustatory Stimuli? 3.5 Stimulus Intensity and Duration Coding in Taste Bud Receptor Cells 3.6 Do Gustatory Sensory Ganglion Neurons Encode Taste? 3.7 Stimulus Intensity Coding in Afferent Fibers and Gustatory Sensory Ganglion Neurons 3.8 Gustatory Sensory Ganglion Neurons: Adaptation and Coding Stimulus Duration 3.9 Gustatory Stimulus Discrimination in the CNS 3.10 Gustatory Stimulus Intensity Coding in the CNS 4 Summary and Caveats References The Role of ATP and Purinergic Receptors in Taste Signaling 1 Neurotransmitters in Taste Buds 2 ATP as the Key Neurotransmitter in Taste Buds 3 Role of Purinergic Receptors in Intrabud Signaling 4 Adenosine, a Product of ATP Hydrolysis, Modulates Sweet Taste via A2B Receptors 5 How Is Taste Function Altered in the Absence of NTPDase2? 6 Translational Implications 7 Conclusions and Perspectives References Pharmacology of the Umami Taste Receptor 1 Discovery of Umami Taste 2 Umami Compounds 2.1 Amino Acid and Derivatives 2.2 Nucleotides 2.3 High Potency Natural and Synthetic Compounds 3 Candidate Receptors for Umami Taste 4 A Validated Receptor for Umami Taste: T1R1/T1R3 5 Kokumi Taste 6 Future Research on Umami Taste References The Application of In Silico Methods on Umami Taste Receptor 1 Introduction 2 Case Study: The Umami Taste Receptor 3 Alignment of Amino Acid Sequences and Molecular Model of T1R1 and T1R3 4 Molecular Docking and Rescoring Procedures 5 Model of the Dimer and Analysis of the Interface Key Interactions 6 Molecular Dynamics Simulations References Pharmacology of TAS1R2/TAS1R3 Receptors and Sweet Taste 1 Introduction 2 Sweet Tastants 3 Sweet Taste Receptor Modulators 4 Structure of the Sweet Taste Receptor 5 Binding Sites at the Sweet Taste Receptor Subunits 6 Canonical Sweet Taste Transduction 7 Potential Additional Transduction Mechanisms for Sweet Compounds 8 Evolutionary Dynamics of the TAS1R2/3 Genes 9 Sensory/Behavioral Testing of Sweet Stimuli 10 In Vitro Assessment of Sweet Compounds and Sweet Taste Receptor Modulators 11 Conclusions/Outlook References Pharmacology of T2R Mediated Host-Microbe Interactions 1 Introduction 1.1 G Protein-Coupled Receptors 1.2 Taste Sensation 1.3 T2R Classification 1.4 T2R G Protein Selectivity and Signaling 2 Extraoral Expression of T2Rs 2.1 T2Rs in Brain, Gut, and Cancers 2.2 T2Rs in Extracellular Vesicles 3 T2R Host-Microbe Interactions 3.1 Bacterial Quorum Sensing Molecules as New Class of Ligands for T2Rs 3.2 AHLs 3.3 AHLs Interaction with T2Rs 3.4 Pharmacological Characterization of AHL-T2R Interactions 3.5 T2R Amino Acids Interacting with QSMs 3.6 Quinolones Interaction with T2Rs 3.7 Autoinducer Peptides (AIP) Interaction with T2Rs 4 T2Rs in Innate Immunity 4.1 Role of T2R38 Genetics in Innate Immunity 4.2 T2R Mediated Innate Immune Responses in Chemosensory and Immune Cells 5 Challenges in T2R Molecular Pharmacology 5.1 T2R Ligand Specificity 5.2 T2R Expression and Detection 6 Conclusion and Future Directions References Bitter Taste Receptors in the Airway Cells Functions 1 Introduction 2 Expression Profile of T2R Subtypes in Multiple Airway Cells 2.1 Expression on Airway Smooth Muscle 2.2 Expression on Various Airway Epithelial Cell Subtypes 2.3 Expression on Airway Immune Cells 3 Mechanisms and Functional Outcomes of T2R Subtypes in Airways 3.1 T2R Signaling Mechanisms in Regulating ASM Contraction and Relaxation 3.2 T2R Activation and Contractile Agonist Specific Regulation of ASM Function 3.3 T2R Activation in the Regulation of ASM Cell Proliferation 3.4 T2Rs Signaling Mechanisms in Epithelial Cell Subtypes 3.5 Functional Outcomes of T2Rs Activation in the Airway Epithelium 4 T2Rs in Lung Health and Disease: Focus on Features of Allergic Asthma 5 Summary and Future Directions References Mechanisms for the Sour Taste 1 Introduction 2 Search for the Sour Receptor 3 Identification of the Sour Taste Receptor 4 The Sour-Sensing Pathway 5 Other Roles for ``Sour´´ TRCs 6 Perspectives and Open Questions References Cellular and Molecular Mechanisms of Fat Taste Perception 1 Introduction 2 Orosensory Detection of Dietary Fat 2.1 Experimental Evidences 2.2 Clinical Evidences 3 Fat Taste Receptors 3.1 CD36 3.2 GPCR 3.3 Delayed Rectifying Potassium Channels 4 Fat Taste Signaling 5 CD36 and GPR120 Play Alternative Roles 6 Dietary Fatty Acids Activate Tongue-Brain-Gut Loop 7 Fat Taste and Obesity 7.1 Altered Functions of Fat Receptors 7.2 Genetic and Epigenetic Modifications of Fat Receptors 8 Fat Taste Regulation 9 Conclusions and Challenges References Immune Regulatory Roles of Cells Expressing Taste Signaling Elements in Nongustatory Tissues 1 Introduction 2 Intestinal Tuft Cells in Type 2 Immunity 2.1 Intestinal Tuft Cells Express Taste Signaling Elements 2.2 Intestinal Tuft Cells Detect Gut-Dwelling Worms 2.3 Succinate Activates Intestinal Tuft Cells 2.4 Tuft-Cell-Secreted IL25, Leukotrienes, Prostaglandins, and Other Effectors Coordinately Trigger Type 2 Immunity 2.5 Mechanisms Underlying Tuft Cell Hyperplasia in Response to Worm Infection 3 Taste GPCRs and Their Downstream Signaling Elements in the Regulation of Gut Inflammation 4 SCCs in the Airway Act as Sentinel Cells to Coordinate Host Defense 5 Taste GPCRs and Their Downstream Signaling Elements in Gingival Tissues and Their Connections to Periodontitis and Dental Ca... 6 Taste GPCRs and Their Downstream Signaling Elements in Immune Cells and Organs 7 Conclusion References Assessment of Taste Function 1 Introduction 2 Before Taste Testing 3 Psychophysical Tests 4 Chemogustometry and Electrogustometry 5 Whole-Mouth Testing and Regional Testing 6 Taste Threshold Tests, Taste Identification Tests and Taste Intensity Ratings 6.1 Taste Threshold Tests 6.2 Taste Identification Tests 6.3 Taste Intensity Tests 7 Tests Based on Electrophysiology, Brain Imaging or Morphological Changes 8 Assessment of Morphological Changes 9 Biopsies 10 Behavioral Methods 11 Why Not Umami? 12 Summary References What Does the Taste System Tell Us About the Nutritional Composition and Toxicity of Foods? 1 Do Taste Qualities Provide Meaningful Information about the Nutritional Value and Toxicity of Foods? 1.1 Approach 1.2 Sweet Taste 1.3 Salty Taste 1.4 Sour Taste 1.5 Bitter Taste 1.6 Umami Taste 1.7 Fat Taste 1.8 Calcium Taste 2 Taste Is Just One Component of Flavor 3 Some Foods Promote Intake by Activating Post-Oral Nutrient Sensors 4 Conclusions References