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Cellular and Molecular Life Sciences :... Nov 2016Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided... (Review)
Review
Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.
Topics: Amino Acid Sequence; Animals; Disease; Humans; Immunity; Immunomodulation; Signal Transduction; Substance P
PubMed: 27314883
DOI: 10.1007/s00018-016-2293-z -
International Journal of Molecular... Mar 2023The skin, including the hypodermis, is the largest body organ and is in constant contact with the environment. Neurogenic inflammation is the result of the activity of... (Review)
Review
The skin, including the hypodermis, is the largest body organ and is in constant contact with the environment. Neurogenic inflammation is the result of the activity of nerve endings and mediators (neuropeptides secreted by nerve endings in the development of the inflammatory reaction in the skin), as well as interactions with other cells such as keratinocytes, Langerhans cells, endothelial cells and mast cells. The activation of TRPV-ion channels results in an increase in calcitonin gene-related peptide (CGRP) and substance P, induces the release of other pro-inflammatory mediators and contributes to the maintenance of cutaneous neurogenic inflammation (CNI) in diseases such as psoriasis, atopic dermatitis, prurigo and rosacea. Immune cells present in the skin (mononuclear cells, dendritic cells and mast cells) also express TRPV1, and their activation directly affects their function. The activation of TRPV1 channels mediates communication between sensory nerve endings and skin immune cells, increasing the release of inflammatory mediators (cytokines and neuropeptides). Understanding the molecular mechanisms underlying the generation, activation and modulation of neuropeptide and neurotransmitter receptors in cutaneous cells can aid in the development of effective treatments for inflammatory skin disorders.
Topics: Humans; Neurogenic Inflammation; Endothelial Cells; Skin; Neuropeptides; Substance P
PubMed: 36902434
DOI: 10.3390/ijms24055001 -
Cell and Tissue Research Jan 2019Substance P (SP) is a highly conserved member of the tachykinin peptide family that is widely expressed throughout the animal kingdom. The numerous members of the... (Review)
Review
Substance P (SP) is a highly conserved member of the tachykinin peptide family that is widely expressed throughout the animal kingdom. The numerous members of the tachykinin peptide family are involved in a multitude of neuronal signaling pathways, mediating sensations and emotional responses (Steinhoff et al. in Physiol Rev 94:265-301, 2014). In contrast to receptors for classical transmitters, such as glutamate (Parsons et al. in Handb Exp Pharmacol 249-303, 2005), only a minority of neurons in certain brain areas express neurokinin receptors (NKRs) (Mantyh in J Clin Psychiatry 63:6-10, 2002). SP is also expressed by a variety of non-neuronal cell types such as microglia, as well as immune cells (Mashaghi et al. in Cell Mol Life Sci 73:4249-4264, 2016). SP is an 11-amino acid neuropeptide that preferentially activates the neurokinin-1 receptor (NK1R). It transmits nociceptive signals via primary afferent fibers to spinal and brainstem second-order neurons (Cao et al. in Nature 392:390-394, 1998). Compounds that inhibit SP's action are being investigated as potential drugs to relieve pain. More recently, SP and NKR have gained attention for their role in complex psychiatric processes. It is a key goal in the field of pain research to understand mechanisms involved in the transition between acute pain and chronic pain. The influence of emotional and cognitive inputs and feedbacks from different brain areas makes pain not only a perception but an experience (Zieglgänsberger et al. in CNS Spectr 10:298-308, 2005; Trenkwaldner et al. Sleep Med 31:78-85, 2017). This review focuses on functional neuronal plasticity in spinal dorsal horn neurons as a major relay for nociceptive information.
Topics: Animals; Chronic Pain; Humans; Memory; Models, Biological; Nerve Net; Nociception; Substance P
PubMed: 30284083
DOI: 10.1007/s00441-018-2922-y -
International Journal of Molecular... Jan 2022Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous... (Review)
Review
Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.
Topics: Animals; Drug Administration Routes; Drug Compounding; Humans; Models, Animal; Neuropeptides; Organ Specificity; Regeneration; Substance P; Wound Healing
PubMed: 35054936
DOI: 10.3390/ijms23020750 -
Respiratory Physiology & Neurobiology Aug 2019Respiratory frequency plasticity is a long-lasting increase in breathing frequency due to a perturbation. Mechanisms underlying respiratory frequency are poorly... (Review)
Review
Respiratory frequency plasticity is a long-lasting increase in breathing frequency due to a perturbation. Mechanisms underlying respiratory frequency are poorly understood, and there is little evidence of frequency plasticity in neonates. This hybrid review/research article discusses available literature regarding frequency plasticity and highlights potential research opportunities. Also, we include data demonstrating a model of frequency plasticity using isolated neonatal rat brainstem-spinal cord preparations. Specifically, substance P (SubP) application induced a long-lasting (>60 min) increase in spontaneous respiratory motor burst frequency, particularly in brainstem-spinal cords with the pons attached; there were no male/female differences. SubP-induced frequency plasticity is dependent on the application pattern, such that intermittent (rather than sustained) SubP applications induce more frequency plasticity. SubP-induced frequency plasticity was blocked by a neurokinin-1 receptor antagonist. Thus, the newborn rat respiratory control system has the capacity to express frequency plasticity. Identifying mechanisms that induce frequency plasticity may lead to novel methods to safely treat breathing disorders in premature and newborn infants.
Topics: Animals; Animals, Newborn; Brain Stem; Growth and Development; Neuronal Plasticity; Neurotransmitter Agents; Rats; Respiratory Rate; Spinal Cord; Substance P
PubMed: 31055188
DOI: 10.1016/j.resp.2019.04.014 -
Frontiers in Endocrinology 2020Substance P (SP) is a neuropeptide that is released from sensory nerve endings and is widely present in nerve fibers. It acts on bones and related tissues by binding to... (Review)
Review
Substance P (SP) is a neuropeptide that is released from sensory nerve endings and is widely present in nerve fibers. It acts on bones and related tissues by binding to receptors, thereby regulating bone metabolism, cartilage metabolism, and fracture healing. SP has attracted widespread attention as a signaling substance that can be recognized by both the immune system and the nervous system. Previous studies have shown that bone and chondrocytes can synthesize and secrete sensory neuropeptides and express their receptors, and can promote proliferation, differentiation, apoptosis, matrix synthesis, and the degradation of target cells through autocrine/paracrine modes. In this paper, we review the research progress made in this field in recent years in order to provide a reference for further understanding the regulatory mechanism of bone and cartilage physiology and pathological metabolism.
Topics: Animals; Apoptosis; Bone and Bones; Cartilage; Cell Differentiation; Humans; Substance P
PubMed: 32180759
DOI: 10.3389/fendo.2020.00077 -
International Journal of Cardiology Jan 2014The tachykinin, substance P, is found primarily in sensory nerves. In the heart, substance P-containing nerve fibers are often found surrounding coronary vessels, making... (Review)
Review
The tachykinin, substance P, is found primarily in sensory nerves. In the heart, substance P-containing nerve fibers are often found surrounding coronary vessels, making them ideally situated to sense changes in the myocardial environment. Recent studies in rodents have identified substance P as having dual roles in the heart, depending on disease etiology and/or timing. Thus far, these studies indicate that substance P may be protective acutely following ischemia-reperfusion, but damaging long-term in non-ischemic induced remodeling and heart failure. Sensory nerves may be at the apex of the cascade of events leading to heart failure, therefore, they make a promising potential therapeutic target that warrants increased investigation.
Topics: Animals; Heart; Heart Failure; Humans; Sensory Receptor Cells; Substance P; Ventricular Remodeling
PubMed: 24286592
DOI: 10.1016/j.ijcard.2013.11.010 -
British Journal of Pharmacology Dec 2019The article has been co-published with permission in British Journal of Dermatology and British Journal of Pharmacology. The articles are identical except for minor...
The article has been co-published with permission in British Journal of Dermatology and British Journal of Pharmacology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.
Topics: Antipruritics; Humans; Pruritus; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Receptors, Neurokinin-1; Substance P
PubMed: 31612462
DOI: 10.1111/bph.14865 -
Frontiers in Immunology 2021Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by...
Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.
Topics: Aged; Apoptosis; Calcitonin Gene-Related Peptide; Cartilage, Articular; Cells, Cultured; Chondrocytes; Female; Humans; Male; Middle Aged; Osteoarthritis; Signal Transduction; Substance P
PubMed: 34512650
DOI: 10.3389/fimmu.2021.722884 -
International Journal of Molecular... Mar 2019Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in... (Review)
Review
Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.
Topics: Animals; Calcium Channels; Humans; Nociception; Potassium Channels; Substance P
PubMed: 30935032
DOI: 10.3390/ijms20071596