Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concept of neuro-immuno-cutaneous system (NICS) means narrow interrelations between nervous system, immunity and skin. Indeed, there are numerous cellular contacts between nerve fibers, cutaneous cells and immune cells; cutaneous cells can synthesize neuromediators and they express receptors to these molecules; neuromediators are able to modulate functions of cutaneous and/or immune cells. Using confocal or electron microscopy, connexions between nerve fibers and cutaneous cells have been observed. In the skin, nerve fibers may secrete neuromediators: substance P, vaso-active intestinal peptide (VIP), somatostatin, calcitonin-gene related peptide (CGRP), gastrin-releasing peptide (GRP), neuropeptide Y, peptide histidine-isoleucine (PHI), neurotensin, neurokinins A et B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melano-stimulating hormone (MSH) or adreno-corticotrophic hormone (ACTH) are also expressed in the skin. Neuromediators and neurohormones are also secreted by cutaneous cells and these cells express receptors. Functions of epidermal or dermal cells are modulated by these substances. Immune cells transiently present in the skin (macrophages, lymphocytes...) are modulated by neuromediators through receptors. In the course of skin diseases, especially inflammatory diseases, the NICS is destabilized. Psoriasis and atopic dermatitis are good examples. This phenomenon might be due to inflammation but is also responsible for induction and maintenance of the inflammation.
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PMID:[Neuro-immuno-cutaneous system (NICS)]. 915 66

Substance P has various immunomodulatory effects, including in vitro modification of lymphocyte proliferation and cytokine release. Elevated levels of substance P and increased staining of substance P-positive nerve fibres have been reported in atopic dermatitis patients. We examined fluoresceinated substance P binding to a range of lymphocyte subsets and compared the results in atopic dermatitis, non-atopic psoriasis patients and normal controls. Fluoresceinated substance P and phycoerythrin-labelled monoclonal antibodies to CD3, CD4, CD8, CD57, CD19 and CD14 were incubated in duplicate with Ficoll-Hypaque separated peripheral blood mononuclear leukocytes. With flow cytometry the fluoresceinated substance P-positive cells were identifiable as a peak of positively fluorescent cells, and the percentages of positive cells were measured. We have demonstrated binding of fluoresceinated substance P to all subsets examined, with significantly less binding to atopic dermatitis CD3-, CD8- and CD57-positive cells. This may affect cytokine release and hence be important in the pathogenesis of atopic dermatitis.
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PMID:Substance P binding to peripheral blood mononuclear leukocytes in atopic dermatitis. 922 14

Neuropeptides (NP) are a heterogeneous group of proteins functioning as neurotransmitters, neuromodulators and neurohormones. More than fifty of these molecules have been described, and some have been detected in human skin through immunochemistry and radioimmunoassay. In this article we attempt to study the role played by some of these substances such as substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (S), and neurotensin (N). Several NP induce inflammatory response with edema and erythema. They can also induce the release of histamine by mastocytes, regulate cutaneous blood flow, and participate in sweat regulation and nociception. They also exert their action over several cells that participate in immunity, acting as mitotic, and chemotactic factors, inhibiting or stimulating inflammatory mechanisms. Specific NP have their receptors on epidermal cells. We will also try to study certain diseases in which NP play an important role in inducing or alleviating lesions, such as psoriasis, atopic eczema, alopecia areata, vitiligo, nodular prurigo, aquagenic pruritus, hypertrophic scars and other entities.
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PMID:[Role of neuropeptides in dermatology]. 927 66

The presence of neuropeptides and their specific receptors has been detected in the skin and the epithelial tissues. They are involved in innervation, immunomodulation, glandular secretion, control of cellular proliferation and regulation of blood flow. The fact that they act in so many different ways means that neuropeptides and their agonists and antagonists are now being regarded as potential therapeutic agents in dermatologic diseases. Among the substances which act as antagonists, particular attention should be paid to capsaicin, which has therapeutic potential for three types of indication: peripheral neurologic pain, affections with a neurogenic inflammatory component and pruriginous dermatosis; peptide T with therapeutic potential for psoriasis; and spantide, which might prove useful in dermatoses related to substance P. The influence of topical corticosteroids on the mechanism of action of neuropeptides can explain its efficacy in the treatment of many dermatoses. Among the agonists, the possibility of taking advantage of the vasodilatory activity of the calcitonin gene-related peptide is being considered in Raynaud's disease and erectile disfunction of the penis; and the immunomodulatory and anti-inflammatory action of the alpha-melanocyte stimulating hormone is being studied as a potential means of controlling inflammatory dermatoses of immunological origin.
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PMID:[Neuropeptides in dermatologic therapy]. 927 77

Mast cells are involved in atopic disorders, often exacerbated by stress, and are located perivascularly close to sympathetic and sensory nerve endings. Mast cells are activated by electrical nerve stimulation and millimolar concentrations of neuropeptides, such as substance P (SP). Moreover, acute psychological stress induces CRH-dependent mast cell degranulation. Intradermal administration of rat/human CRH (0.1-10 microM) in the rat induced mast cell degranulation and increased capillary permeability in a dose-dependent fashion. The effect of CRH on Evans blue extravasation was stronger than equimolar concentrations of the mast cell secretagogue compound 48/80 or SP. The free acid analog of CRH, which does not interact with its receptors (CRHR), had no biological activity. Moreover, systemic administration of antalarmin, a nonpeptide CRHR1 antagonist, prevented vascular permeability only by CRH and not by compound 48/80 or SP. CRHR1 was also identified in cultured leukemic human mast cells using RT-PCR. The stimulatory effect of CRH, like that of compound 48/80 on skin vasodilation, could not be elicited in the mast cell deficient W/Wv mice but was present in their +/+ controls, as well as in C57BL/6J mice; histamine could still induce vasodilation in the W/Wv mice. Treatment of rats neonatally with capsaicin had no effect on either Evans blue extravasation or mast cell degranulation, indicating that the effect of exogenous CRH in the skin was not secondary to or dependent on the release of neuropeptides from sensory nerve endings. The effect of CRH on Evans blue extravasation and mast cell degranulation was inhibited by the mast cell stabilizer disodium cromoglycate (cromolyn), but not by the antisecretory molecule somatostatin. To investigate which vasodilatory molecules might be involved in the increase in vascular permeability, the CRH injection site was pretreated with the H1-receptor antagonist diphenhydramine, which largely inhibited the CRH effect, suggesting that histamine was involved in the CRH-induced vasodilation. The possibility that nitric oxide might also be involved was tested using pretreatment with a nitric oxide synthase inhibitor that, however, increased the effect of CRH. These findings indicate that CRH activates skin mast cells at least via a CRHR1-dependent mechanism leading to vasodilation and increased vascular permeability. The present results have implications for the pathophysiology and possible therapy of skin disorders, such as atopic dermatitis, eczema, psoriasis, and urticaria, which are exacerbated or precipitated by stress.
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PMID:Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. 942 40

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance (P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis.
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PMID:Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis. 944 83

Connections between nerve fibres and cutaneous cells have been studied using confocal and electron microscopy. In the skin, nerve fibres may secrete neuromediators, i.e. substance P, vasoactive intestinal peptide, somatostatin, calcitonin-gene-related peptide, gastrin-releasing peptide, neuropeptide Y, peptide histidine-isoleucine, neurotensin, neurokinins A and B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melanocyte-stimulating hormone and adrenocorticotrophic hormone are also expressed in the skin. Neuromediators and neurohormones may be secreted by cutaneous cells, which also express receptors. Functions of epidermal and dermal cells are modulated by these substances. Immune cells transiently present in the skin (e.g. macrophages and lymphocytes) are modulated by neuromediators through receptors. During the course of skin disorders, especially inflammatory reactions, the neuroimmunocutaneous system is destabilized. This is particularly true in psoriasis. This destabilization may be secondary, although evidence shows it can also be responsible for the induction and maintenance of the inflammatory process. The skin, the nervous system and immunity are not independent systems but are closely associated and use the same language of cytokines and neurotransmitters. A new concept is suggested: the neuroimmunocutaneous system.
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PMID:Skin, immunity and the nervous system. 947 Aug 98

Many investigators have reported proliferation of terminal cutaneous nerves and upregulation of various neuropeptides (substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide) in psoriatic lesions. Nerve growth factor promotes growth of nerves and causes upregulation of neuropeptides like substance P and calcitonin gene-related peptide. In this study we investigated the expression of nerve growth factor in psoriatic lesions, non-lesional psoriatic skin, lichen planus and normal control skin. Immunoperoxidase staining was applied on cryosections prepared from snap-frozen biopsy specimens. The primary antibody used was a polyclonal anti-NGF-beta antibody. Nerve growth factor was detected only in the keratinocytes. In psoriatic tissue the number of keratinocytes per square millimeter of epidermis positive for nerve growth factor was 84.7 +/- 46.3 compared to 44.8 +/- 29.9, 18.9 +/- 11.8 and 7.5 +/- 16.9, respectively, in non-lesional psoriatic skin, normal skin and lichen planus. Increased expression of nerve growth factor substantiates larger numbers of terminal cutaneous nerves and upregulations of substance P and calcitonin gene-related peptide in psoriatic lesions. In addition, nerve growth factor is mitogenic to keratinocytes, activates T-lymphocytes and can induce migration of inflammatory cellular infiltrates, histological features characteristic of psoriasis.
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PMID:Psoriatic keratinocytes express high levels of nerve growth factor. 953 81

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. It has been observed that certain skin diseases such as psoriasis and atopic dermatitis have a neurogenic component. Neuropeptides released by sensory nerves that innervate the skin and often contact epidermal and dermal cells can directly modulate functions of keratinocytes, Langerhans cells (LC), mast cells, dermal microvascular endothelial cells and infiltrating immune cells. Among these neuropeptides the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) have been reported to effectively modulate skin and immune cell functions such as cell proliferation, cytokine production or antigen presentation under physiological or pathophysiological conditions. Expression and regulation of their corresponding receptors that are expressed on a variety of skin cells as well as the presence of neuropeptide-specific peptidases such as neutral endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final biological response mediated by these peptides on the target cell or tissue. Likewise, skin cells like keratinocytes or fibroblasts are a source for neurotrophins such as nerve growth factor that are required not only for survival and regeneration of sensory neurons but also to control responsiveness of these neurons to external stimuli. Therefore, neuropeptides, neuropeptide receptors, neuropeptide-degrading enzymes and neurotrophins participate in a complex, interdependent network of mediators that modulate skin inflammation, wound healing and the skin immune system. This review will focus on recent studies demonstrating the role of tachykinins, CGRP, SOM and VIP and their receptors and neuropeptide-degrading enzymes in mediating neurogenic inflammation in the skin.
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PMID:Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. 958 47

Urocortin (Ucn) is related to corticotropin-releasing hormone (CRH), and both are released in the brain under stress where they stimulate CRH 1 and 2 receptors (CRHR). Outside the brain, they may have proinflammatory actions through activation of mast cells, which are located perivascularly close to nerve endings and degranulate in response to acute psychological stress. Here, we report that a concentration of intradermal Ucn as low as 10 nM induced dose-dependent rat skin mast cell degranulation and increased vascular permeability. This effect appeared to be equipotent to that of calcitonin gene-related peptide and neurotensin. Ucn-induced skin vasodilation was inhibited by pretreatment with the mast cell stabilizer disodium cromoglycate (cromolyn) and was absent in the mast cell-deficient W/Wv mice. The selective nonpeptide CRH receptor 1 antagonist, antalarmin and the nonselective peptide antagonist astressin both reduced vascular permeability triggered by Ucn but not that by Substance P or histamine. In contrast, the peptide antagonist alpha-helical CRH-(9-41) reduced the effect of all three. The vasodilatory effect of Ucn was largely inhibited by pretreatment with H1 receptor antagonists, suggesting that histamine is the major mediator involved in vitro. Neuropeptide depletion of sensory neurons, treatment with the ganglionic blocker hexamethonium, or in situ skin infiltration with the local anesthetic lidocaine did not affect Ucn-induced vascular permeability, indicating that its in situ effect was not mediated through the peripheral nervous system. These results indicate that Ucn is one of the most potent triggers of rat mast cell degranulation and skin vascular permeability. This effect of Ucn may explain stress-induced disorders, such as atopic dermatitis or psoriasis, and may lead to new forms of treatment.
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PMID:Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors. 1002 77


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