Substance P
From Pain to Cancer
- 1st Edition - November 6, 2024
- Editor: Robert Vink
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 2 2 1 9 4 - 1
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 2 2 1 9 5 - 8
Substance P: From Pain to Cancer, a volume in the Molecular Mediators in Health and Disease: How Cells Communicate series, provides a complete discussion of substance P biology,… Read more
Purchase options
Institutional subscription on ScienceDirect
Request a sales quoteSubstance P: From Pain to Cancer, a volume in the Molecular Mediators in Health and Disease: How Cells Communicate series, provides a complete discussion of substance P biology, its role in normal physiology and a variety of diseases.
The volume provides an introduction to substance P and its pharmacology, followed by exploring its role across the human body including cardiovascular function, micturition, learning and memory, emesis, respiration and sleep. It then discusses the critical role of substance P in several disease states including acute brain injury, neurodegeneration, seizures, depression and anxiety, cancer, musculoskeletal disorders, and viral infection, including COVID-19. The book closes with a look towards future perspectives for substance P.
Substance P: From Pain to Cancer is an ideal reference for researchers across the life sciences interested in understanding the role of this multi-functioning mediator and its biological significance.
The volume provides an introduction to substance P and its pharmacology, followed by exploring its role across the human body including cardiovascular function, micturition, learning and memory, emesis, respiration and sleep. It then discusses the critical role of substance P in several disease states including acute brain injury, neurodegeneration, seizures, depression and anxiety, cancer, musculoskeletal disorders, and viral infection, including COVID-19. The book closes with a look towards future perspectives for substance P.
Substance P: From Pain to Cancer is an ideal reference for researchers across the life sciences interested in understanding the role of this multi-functioning mediator and its biological significance.
- Provides a comprehensive overview of the role of substance P across different organ systems, including the nervous, cardiovascular and musculoskeletal systems and renal function
- Includes detailed coverage of the specific actions of substance P in various disease states and conditions, such as inflammation, cancer, acute brain injury, mood disorders, Parkinson’s disease, Alzheimer’s disease and viral infection including COVID-19
- Examines substance P as a modulator of the immune response and pain perception
- Includes expertise from a range of interdisciplinary areas including molecular biology, pharmacology, physiology, neuroscience, anatomy, and therapeutics
From graduate students to expert level.
- Substance P
- Cover image
- Title page
- Table of Contents
- Front Matter
- Copyright
- Contributors
- Preface
- Series preface
- Chapter 1 The synthesis, release, and binding of substance P
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P synthesis
- 3 Substance P release
- 4 Substance P binds to neurokinin receptors
- 5 Substance P binding activates a variety of signaling pathways
- 6 Regulation of substance P/NK-1 receptor activity
- 7 Conclusion
- References
- Chapter 2 Distribution of substance P receptors in mammals
- Abstract
- Keywords
- 1 Introduction
- 2 NK1R
- 2.1 Biochemical and phylogenetic characteristics of NK1R
- 2.2 Tissue distribution of NK1R in mammals
- 3 MRGPRX2 (MRGX2)
- 3.1 Biochemical and phylogenetic characteristics of MRGPRX2 (MRGX2)
- 3.2 Tissue-distribution of MRGPRX2 in human and MrgprB2 in mice
- 4 Conclusion and perspectives
- References
- Chapter 3 Substance P in nonmammalian biology: Evolutionarily conserved tachykinin signaling
- Abstract
- Keywords
- Acknowledgments
- 1 Introduction
- 2 Tachykinins and their receptors in mammals
- 3 Tachykinins and their receptors in deuterostome invertebrates and protochordates
- 4 Tachykinins and their receptors in nonmammalian vertebrates
- 4.1 TK signaling in cephalochordates and agnate chordates
- 4.2 TK signaling in elasmobranchs (sharks)
- 4.3 TK signaling in teleost fish
- 4.4 Tachykinin signaling in amphibians
- 5 Tachykinins and their receptors in protostome invertebrates
- 5.1 Identification of invertebrate tachykinin precursors and receptors
- 5.2 Distribution and functions of tachykinins in invertebrates
- 5.3 Functional roles of TK signaling in Drosophila
- 5.4 Invertebrate gland tachykinins as secreted toxins or vasodilatory factors
- 5.5 A case of novel ligands for an insect TK receptor and a case of promiscuity
- 5.6 Natalisins, a sister group of tachykinins in arthropods
- 6 Conserved roles of tachykinin signaling in the animal kingdom
- 7 Notes on the evolution of tachykinin signaling
- 8 Conclusions and perspectives
- 9 Summary
- References
- Chapter 4 Methodological foundations of substance P detection
- Abstract
- Keywords
- 1 Introduction
- 2 SP measurement: Handling of blood sample
- 3 SP measurements from tissues
- 3.1 Sample obtaining
- 3.2 Sample preparation
- 3.3 Solid-phase extraction (SPE)
- 4 Detection by radioimmunoassay (RIA) and enzyme immunoassay (EIA)
- 5 Effects of protease inhibitor cocktail in EIA
- 6 Differentiation of neuronal and nonneuronal SP levels
- 7 Immunohistochemical detection
- 8 Measurement of SP in tears
- 9 SP levels in other body secretions
- 10 Conclusion
- References
- Chapter 5 Substance P receptor antagonists
- Abstract
- Keywords
- 1 Introduction
- 2 Ligands of the neurokinin-1 receptor
- 2.1 Neurokinin-1 receptor is the high-affinity receptor for substance P
- 2.2 The design and synthesis of peptide and nonpeptide neurokinin-1 receptor antagonists
- 2.3 The neurokinin-1 receptor antagonist’s binding sites
- 3 Current medical use of neurokinin-1 receptor antagonists
- 3.1 Neurokinin-1 receptor antagonists as antiemetics
- 3.2 Studies in other pathologies
- 3.3 Features of neurokinin-1 receptor antagonists worth considering for broader clinical use
- 4 Concluding remarks
- References
- Chapter 6 Substance P in the cardiovascular system
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P in the heart
- 2.1 Localization of SP in the heart
- 2.2 SP receptors
- 2.3 Function of SP in the heart
- 3 Substance P in the vascular system
- 3.1 Localization of members of the SP signaling system in the vessels
- 3.2 Effects of SP on the vessels of the bloodstream
- 4 Effect of SP on the control of cardiovascular system functions
- 5 Conclusion
- References
- Chapter 7 Substance P in lower urinary tract function and dysfunction
- Abstract
- Keywords
- 1 Introduction
- 1.1 Overview
- 1.2 Neural circuits in control of urinary continence and micturition
- 2 Effects of capsaicin on substance P in micturition
- 3 Bladder function in neonates and preprotachykinin A gene deletion
- 3.1 Bladder function in neonates
- 3.2 Preprotachykinin A gene deletion
- 4 Components of the urinary system that control lower urinary tract function
- 4.1 Bladder
- 4.2 Urethra
- 4.3 Ganglionic neurons
- 4.4 Spinal cord
- 4.5 Supraspinal regions
- 5 Effects of systemic administration of NK1 antagonist in animals
- 6 Pathophysiological changes in the lower urinary tract
- 6.1 Animal models of lower urinary tract dysfunction
- 6.2 Lower urinary tract dysfunction in humans
- 7 Clinical trials
- 7.1 Serlopitant
- 7.2 Aprepitant
- 7.3 Cizolirtine
- 8 Concluding remarks
- References
- Chapter 8 Role of the substance P in learning and memory
- Abstract
- Keywords
- 1 Introduction
- 2 Nonassociative learning—Habituation and sensitization
- 3 Simple associative learning—Classical conditioning
- 4 Simple associative learning—Operant conditioning
- 5 Memory for innate behavioral sequences
- 6 Memory for learned behavioral sequences
- 7 Summary and conclusion
- References
- Chapter 9 Substance P in nausea and vomiting
- Abstract
- Keywords
- Acknowledgments
- 1 Introduction
- 1.1 Nausea and vomiting in health, disease and therapy
- 1.2 A brief overview of nausea and vomiting physiology and pharmacology
- 2 Links between substance P, nausea and vomiting
- 2.1 Induction of vomiting by exogenous SP and related tachykinins in preclinical models
- 2.2 Actions of tachykinins on the digestive tract potentially contributing to the induction of nausea and vomiting and associated GI motor events
- 2.3 Presence of SP and NK1 receptors in neural pathways implicated in nausea and vomiting
- 2.4 Release of SP by emetic stimuli in humans and animals
- 3 Vomit-blocking effects of NK1 receptor antagonists and studies with antagonists at other tachykinin receptors
- 3.1 Preclinical studies of NK1RAs in species with a vomiting reflex
- 3.2 Are NK2 and NK3 receptors involved in vomiting?
- 3.3 Some challenges of species differences in studying the antivomiting effects of NK1RAs
- 4 Clinical efficacy of NK1 receptor antagonists
- 4.1 Spectrum of efficacy
- 5 Site(s) of action
- 6 Concluding comments
- References
- Chapter 10 Substance P in the central control of respiration
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P in the control of breathing
- 3 Localization of substance P and neurokinin receptors
- 4 Cellular actions within central respiratory sites
- 5 Physiological role(s) of substance P in the control of breathing
- 6 Chemosensitivity
- 7 The broader role of neuromodulation in the orchestration of behavioral functions
- References
- Chapter 11 Substance P in bone metabolism
- Abstract
- Keywords
- 1 Introduction
- 1.1 Bone structure
- 1.2 Bone metabolism
- 2 Substance P and bone cells
- 2.1 Substance P and osteoclasts
- 2.2 Substance P and osteoblasts
- 2.3 Substance P and osteocytes
- 3 Substance P and bone metabolism
- 3.1 Health
- 3.2 Trauma
- 3.3 Disease—Osteoporosis
- 4 Conclusion
- References
- Chapter 12 Life without substance P: The naked mole rat
- Abstract
- Keywords
- Acknowledgments
- 1 Introduction
- 1.1 Pain and itch
- 2 Reduced or absent sensitivity to elevated CO2 and fumes from other irritants
- 3 Lack of pulmonary edema from hypercapnia
- 4 Pain responses
- 4.1 Lack of cutaneous pain from capsaicin and rescue with extrinsic substance P
- 4.2 Lack of cutaneous pain from acid but no rescue with extrinsic substance P
- 4.3 Reduced inflammatory pain in the formalin test and rescue with extrinsic substance P
- 4.4 Normal pain behavior to acute mechanical and acute heat stimuli
- 5 Lack of itch from histamine and rescue with extrinsic substance P
- 6 Discussion
- References
- Chapter 13 Substance P in inflammation
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P augments the inflammatory responses of immune cells
- 2.1 Monocytes, macrophages, and dendritic cells
- 2.2 Mast cells
- 2.3 Granulocytes
- 2.4 Lymphocytes
- 3 Substance P augments tissue-specific inflammatory responses
- 3.1 The gastrointestinal tract
- 3.2 The central nervous system and eye
- 3.3 Skin and respiratory tract
- 3.4 Bone and joint tissue
- 4 Concluding remarks
- References
- Chapter 14 Substance P in oxidative stress
- Abstract
- Keywords
- 1 Introduction
- 1.1 Oxidative stress
- 1.2 The interactions between substance P and oxidative stress
- 2 ROS-inducing property of SP
- 2.1 ROS-inducing property of SP: Implication in pulmonary disorders
- 2.2 ROS-inducing property of SP: Implication in brain-related disorders
- 2.3 ROS-inducing property of SP: Implication in cardiac impairment
- 2.4 ROS-inducing property of SP: Implication in psychological stress
- 3 ROS-scavenging property of SP
- 3.1 ROS-scavenging property of SP: Implication in diabetic complications
- 4 The redox-regulatory effects of SP/NK1R signaling in cancer
- 5 Concluding remarks
- References
- Chapter 15 Substance P in pain
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P in pain
- 2.1 Nociceptive effects
- 2.2 Antinociceptive effects
- 2.3 Genetic studies
- 3 NK1 antagonists in pain
- 3.1 Preclinical studies
- 3.2 Clinical translation
- 4 Conclusion
- References
- Chapter 16 Substance P in cancer
- Abstract
- Keywords
- Conflict of interest
- 1 Introduction
- 1.1 Cancer global problem
- 1.2 Substance P and neurokinin-1 receptor are involved in cancer
- 2 SP and NK-1R in tumors
- 2.1 SP
- 2.2 SP hydrolysis
- 2.3 NK-1R
- 3 Substance P is involved in many types of signaling in cancer
- 4 SP/NK-1R system a predictive factor in cancer
- 5 SP increases the proliferation of cancer cells (mitogenesis) and induces antiapoptotic effect in cancer cells
- 6 SP Warburg effect
- 7 SP angiogenesis in cancer
- 8 SP in invasion and metastasis
- 8.1 Blebbing
- 8.2 The ECM
- 8.3 Metastatic brain cancer
- 8.4 Surgical intervention promotes SP-mediated recurrence and metastasis
- 9 SP is involved in risk of lung cancer after long-term use of angiotensin-converting enzyme
- 10 NK-1R antagonist in cancer therapy
- 10.1 NK-1R antagonists
- 10.2 NK-1R antagonist mechanism of action as antitumor activity
- 10.3 The reversal of tumor chemotherapy resistance and decreasing chemotherapy toxicity
- 10.4 Combination therapy of chemotherapy and NK-1R antagonists
- 10.5 Safety and therapeutic human use
- 10.6 Dose of aprepitant as an antitumor drug
- 11 Concluding remarks
- References
- Chapter 17 Substance P in cardiac dysfunction
- Abstract
- Keywords
- Acknowledgments
- 1 Introduction
- 2 Localization of substance P in the heart
- 3 Substance P regulation of normal cardiac physiology
- 4 Substance P in cardiac disease
- 4.1 Studies using substance P deletion in mice
- 4.2 Studies using administration of exogenous substance P
- 4.3 Studies using neurokinin 1 receptor antagonists
- 5 Cellular effects of substance P
- 5.1 Cardiomyocytes
- 5.2 Cardiac fibroblasts
- 5.3 Macrophages and mast cells
- 6 Priority areas for future research
- 6.1 Translational studies
- 6.2 Substance P receptors
- 7 Summary and conclusion
- References
- Chapter 18 Substance P in neurotrauma
- Abstract
- Keywords
- Acknowledgment
- 1 Introduction
- 2 Evidence for the role of SP following TBI
- 2.1 How does SP drive secondary injury following TBI?
- 2.2 Role of SP in altering BBB permeability and promoting vasogenic edema formation
- 2.3 Role of SP in the inflammatory response postinjury
- 3 Efficacy of NK1 antagonism acutely following TBI
- 4 SP and neurodegeneration post-TBI
- 5 Conclusion
- References
- Chapter 19 Substance P in stroke
- Abstract
- Keywords
- 1 Introduction
- 1.1 Primary injury mechanisms
- 1.2 Secondary injury mechanisms
- 2 Clinical manifestations of secondary injury
- 3 Substance P in stroke
- 4 Therapeutic potential of substance P in stroke
- 5 Future perspectives
- 6 Conclusion
- References
- Chapter 20 Substance P in Alzheimer’s and Parkinson’s disease
- Abstract
- Keywords
- 1 Introduction
- 1.1 Neuroprotection
- 2 Alzheimer’s disease
- 2.1 SP and beta-amyloid toxicity
- 2.2 SP and antiamyloidogenic activity
- 2.3 SP and potassium channels
- 3 Parkinson’s disease
- 3.1 SP and motor symptoms of PD
- 3.2 SP and nonmotor symptoms of PD
- 4 Conclusions
- References
- Chapter 21 Substance P receptor antagonists for major depressive disorder
- Abstract
- Keywords
- 1 Introduction
- 1.1 Challenges of developing a new antidepressant drug
- 1.2 Antidepressant and anxiolytic-like activity of NK1 receptor antagonists in animals
- 1.3 Localization and function of substance P and NK1 receptors in the brain
- 1.4 Antidepressant and anxiolytic efficacy in patients with MDD
- 1.5 Effects of NK1 receptor antagonists on symptoms related to depression
- 1.6 Conclusions: Is there a future for NK1 receptor antagonists in psychiatry?
- References
- Chapter 22 From a putative antidepressant to a validated mouse model of ADHD via NK1 receptors
- Abstract
- Keywords
- Acknowledgment
- 1 Introduction
- 2 NK1R as a target for a new class of putative antidepressants
- 2.1 Changes in serotonergic and noradrenergic transmission in NK1R−/− mice
- 2.2 NK1R−/− mice are hyperactive
- 2.3 An antidepressant drug challenge reduced the locomotor activity of NK1R−/− mice
- 3 What is wrong with NK1R−/− mice?
- 3.1 CNS stimulants prevent the hyperactivity of NK1−/− mice
- 3.2 Dopamine transmission is disrupted in NK1R−/− mice
- 3.3 Genetic studies of NK1R (TACR1) in ADHD patients
- 3.4 Summary
- 4 Are NK1−/− mice a model of ADHD?
- 4.1 NK1R−/− mice are inattentive and impulsive in the 5-choice serial reaction-time test
- 4.2 Effect of NK1R antagonists on cognitive performance of NK1R−/− and wild-type mice
- 4.3 L-type Ca2+ channel (LTCC) blockade modifies cognitive performance of NK1R−/− and wild-type mice
- 4.4 Breeding environment influences premature responses by NK1R−/− mice
- 4.5 Drugs licensed to treat ADHD improve specific aspects of the abnormal behavioral phenotype of NK1R−/− mice
- 4.6 Summary
- 5 NK1R antagonists as antidepressant: Does L-type (Ca2+) channel (LTCC) blockade matter?
- 6 L-type (Ca2+) channel (LTCC) blockade and antidepression
- 7 Conclusion
- References
- Chapter 23 Substance P in stress and anxiety
- Abstract
- Keywords
- 1 Introduction
- 2 Distribution of SP in the brain
- 3 Structure and signaling of SP (NK1) receptors
- 4 Distribution of NK1 receptors in the brain
- 5 Preclinical evidence implicating SP/NK1 receptor signaling in stress and anxiety
- 5.1 Effects of acute and chronic stressors on SP/NK1 receptor signaling
- 5.2 Long-term effects of acute and chronic stressors on SP/NK1 receptor signaling
- 5.3 Effects of modulations of the SP/NK1 receptor system on physiological stress responses
- 5.4 Behavioral responses of laboratory animals after modulation of the SP/NK1 receptor system
- 5.5 Dysregulated SP/NK1 receptor signaling in pathophysiological animal models
- 6 Clinical relevance of the SP/NK1 receptor system in stress and anxiety disorders
- 7 Conclusions
- References
- Chapter 24 Substance P-neurokinin 1 receptor pathway in musculoskeletal disorders
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P has diverse functions
- 2.1 Role of substance P in pain transmission and sensitization
- 2.2 Substance P promotes inflammation and immune cell chemotaxis
- 2.3 Substance P’s role in wound healing (Reparative and fibrotic)
- 3 Substance P has diverse locations and roles in musculoskeletal tissues and disorders
- 3.1 Muscle
- 3.2 Tendon
- 3.3 Bone
- 3.4 Fascial tissues, including the dermis
- 4 Conclusion
- References
- Chapter 25 Substance P and sudden infant death syndrome (SIDS)
- Abstract
- Keywords
- 1 Introduction
- 2 Substance P and the respiratory network in neurodevelopment
- 3 Altered SP neurotransmission in the brainstem of SIDS infants
- 4 Substance P and hypoxia in SIDS
- 5 Substance P and sleep-wake physiology in SIDS
- 6 Summary and future directions
- References
- Chapter 26 Immunobiology and pharmacology of neuropeptide substance P
- Abstract
- Keywords
- 1 Introduction
- 1.1 Substance P
- 1.2 Neurokinin receptors
- 2 Immunology
- 2.1 Substance P and mast cells
- 2.2 Substance P and macrophages
- 2.3 Substance P and T lymphocytes
- 3 Substance P in disease
- 3.1 Infection
- 3.2 Cancer
- 3.3 Autoimmunity
- 4 Pharmacology of substance P and its receptors
- 4.1 Pharmacology of substance P
- 4.2 Drugs targeting SP receptors
- 4.3 Emerging tools for GPCR drug discovery
- 5 Concluding remarks
- References
- Chapter 27 Substance P in viral diseases—Especially coronavirus disease
- Abstract
- Keywords
- Acknowledgments
- 1 Introduction
- 2 Substance P
- 2.1 Orchestrating physiological regulation-Substance P as regulide
- 2.2 Modulation of inflammatory response by Substance P and NK-1Rs
- 2.3 Role of SP in respiration and respiratory disorders
- 3 Substance P and COVID-19: A potential connection
- 3.1 Proposed mechanism of SP action in COVID-19
- 4 Phases of coronavirus disease
- 4.1 Classical symptoms
- 4.2 Neurological manifestations of COVID-19
- 5 SARS-CoV-2 neurological storming by direct invasion
- 5.1 Blood-brain barrier and endothelial cells
- 5.2 Corona spike penetration through endothelial transcytosis
- 5.3 Mitochondrial damage to endothelial cells
- 6 SARS-CoV-2 neurological storming by indirect invasion
- 6.1 BBB leakage by molecular plexus of systemic inflammation
- 6.2 Targeting tight junctions
- 6.3 Targeting endothelial cells
- 6.4 Targeting the NVU
- 6.5 Targeting BEC transporter molecules
- 7 Use of Substance P and fragments in the diagnosis, therapy, and prevention of the corona disease; results and future aspects
- 7.1 Substance P in diagnosis
- 7.2 Substance P in therapy and prevention of COVID-19
- 8 Conclusion
- References
- Chapter 28 Substance P: Perspectives and future directions
- Abstract
- Keywords
- 1 Introduction
- 2 Receptors
- 3 Receptor occupancy
- 4 NK1 receptor antagonists
- 5 Acute vs chronic changes in substance P
- 6 Conclusion
- References
- Index
- No. of pages: 550
- Language: English
- Edition: 1
- Published: November 6, 2024
- Imprint: Academic Press
- Paperback ISBN: 9780443221941
- eBook ISBN: 9780443221958
RV
Robert Vink
Robert Vink is an Emeritus Professor at the University of South Australia and is currently Chair of the Board for Connectivity: Traumatic Brain Injury Australia. He was previously appointed as the Professor and Chair of Neurosurgical Research and Head of School, Medical Sciences at the University of Adelaide, Australia. Throughout his time as a teaching/research academic he led a highly productive research group and maintained an extensive publication output. He is the author of over 260 articles and book chapters. He has supervised more than 30 graduate research students, many of whom now hold significant academic and other positions throughout Australia and internationally.
He is known internationally for his work in traumatic brain injury and has received numerous prestigious awards and appointments related to this. He currently provides research consulting services to universities and the pharmaceutical industry.
Affiliations and expertise
Consultant (Biotechnology, Legal, Higher Education) Vink NeuroConsulting, Mylor, AustraliaRead Substance P on ScienceDirect