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 density and fine structure of the peripheral nerve system in various skin lesions of 64 patients with atopic dermatitis (AD) was quantitatively analyzed by immunohistochemical staining with antibodies directed against protein gene product (PGP) and substance P (SP). The density of PGP-positive peripheral nerves was 2.5 x 10(3) microns2/delta s (delta s = 0.24 mm2 selected area) in early acute lesions, 3.8 x 10(3) microns2/delta s in subacute lesions, 4.9 x 10(3) microns2/delta s in lichenified lesions and 7.1 x 10(3) microns2/delta s in prurigo lesions of AD. The density of nerve fibers in subacute, lichenified and prurigo lesions was significantly higher than in uninvolved skin of AD patients (2.0 x 10(3) microns2/delta s). Electron microscopically, bulging of axons with many mitochondria and a loss of their surrounding sheath of Schwann cells suggests that the free nerve endings in skin lesions of AD are in an active state of excitation. Many pinocytotic vesicles in the periphery of basal keratinocytes facing nerve endings which contained many neurovesicles suggests reciprocal effects between keratinocytes and nerve endings. The number of SP-positive nerve fibers in AD lesions was far less than one-tenth of the number of PGP-positive nerve fibers.
Arch Dermatol Res 1997 Feb
PMID:Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis. 912 59

In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-alpha at a concentration of 10(-7) M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher (P < 0.01) sensitivity towards stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP.
Arch Dermatol Res 1997 Apr
PMID:Functional studies of skin mast cells in lichen planus. 916 35

Substance P (SP) is distributed in both the central and peripheral nervous system. It has various effects on immunocompetent cells, such as macrophages and lymphocytes. The aim of our study was to search for the presence of SP receptors (SP-R) on human cutaneous Langerhans cells (LC), and to determine the effects of SP on LC immunological functions in a model of mixed epidermal cell-lymphocyte reaction (MELR). Radioligand binding studies showed that LC-enriched epidermal cell suspensions reversibly bound SP, and that the specific binding increased with the percentage of LC. Functional assays showed that SP had no effect when added at concentrations from 10(-6) M to 10(-12) M to the MELR. The addition of SP at concentrations of 10(-4) M and 10(-5) M was able to inhibit the allogeneic T-cell response (98.3 +/- 1.8% and 92.8 +/- 8.9% inhibition, respectively) without modifying the cell viability. This inhibition was through an effect of SP on both T-cell and LC function. We conclude that SP has receptors on LC and may inhibit antigen presentation.
Arch Dermatol Res 1997 Apr
PMID:Binding and in vitro modulation of human epidermal Langerhans cell functions by substance P. 916 39

Close contacts between mast cells (MC) and nerve fibers have previously been demonstrated in normal and inflamed skin by light and electron microscopy. A key step for any study in MC-nerve interactions in situ is to simultaneously visualize both communication partners, preferably with the option of double labelling the nerve fibers. For this purpose, we developed the following triple-staining technique. After paraformaldehyde-picric acid perfusion fixation, cryostat sections of back skin from C57BL/6 mice were incubated with a primary rat monoclonal antibody to substance P (SP), followed by incubation with a secondary goat-anti-rat TRITC-conjugated IgG. A rabbit antiserum to CGRP was then applied, followed by a secondary goat-anti-rabbit FITC-conjugated IgG. MCs were visualized by incubation with AMCA-labelled avidin, or (for a more convenient quantification of close MC-nerve fiber contacts) with a mixture of TRITC- and FITC-labelled avidins. Using this simple, novel covisualization method, we were able to show that MC-nerve associations in mouse skin are, contrary to previous suggestions, highly selective for nerve fiber types, and that these interactions are regulated in a hair cycle-dependent manner: in telogen and early anagen skin, MCs preferentially contacted CGRP-immunoreactive (IR) or SP/CGRP-IR double-labelled nerve fibers. Compared with telogen values, there was a significant increase in the number of close contacts between MCs and tyrosine hydroxylase-IR fibers during late anagen, and between MCs and peptide histidine-methionine-IR and choline acetyl transferase-IR fibers during catagen.
Arch Dermatol Res 1997 Apr
PMID:A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle--dependent changes in mast cell--nerve fiber contacts in murine skin. 916 40

We present a case of follicular cystic hamartoma, a distinctive cutaneous malformation characterized by marked overgrowth of folliculosebaceous units accompanied by appreciable mesenchymal alterations, including fibroplasia, increased vascular components, and numerous adipocytes. A conspicuous feature of our case is an aggregation of thick trespassing nerve bundles in the deep portion of the neoplasm. An immunohistochemical study revealed the nerve bundles were immunoreactive for the general neuronal marker protein gene product 9.5. The nerves, however, stained negatively with antibodies against neuropeptides such as calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide, and neuropeptide Y, all of which are known to be contained in normal cutaneous nerves. The presence of these aberrant nerve bundles devoid of the normal expression of neuropeptides supports the concept that folliculosebaceous cystic hamartoma is a true, tumor-like malformation characterized by abnormal overgrowth of normal components of the skin.
J Dermatol 1997 Jul
PMID:Folliculosebaceous cystic hamartoma with a neural component: an immunohistochemical study. 926 5

As a first line of defence, the skin is equipped with a complex and interactive nerve fibre system to detect irritants and maintain homeostasis. The dermal component of this fibre network has been well characterized and fibres are known to extend throughout the viable epidermis as free nerve endings. To date, this epidermal component remains poorly characterized. We have visualized human volar forearm epidermal nerve fibres by laser-scanning confocal microscopy using the pan-neuronal marker, protein gene-product 9.5 and specific antibodies to substance P. calcitonin gene-related peptide and nerve growth factor. In addition to the varicose free nerve endings, there is a 3-D fibre network in normal human epidermis, with frequent branching of fibres. Branching can be seen to converge on a central trunk apparently extending to the dermis. Thin unmyelinated fibres can be seen in all layers of the viable epidermis. Substance P staining is rarely observed and is much less intense than the protein gene-product 9.5 staining. Calcitonin gene-related peptide and nerve growth factor were not detected in volar forearm epidermis by this method. Pretreatment of the skin in vivo with the neuropharmacological agent, capsaicin, resulted in loss of epidermal fibre staining indicating that these are sensory fibres of the primary C-afferent type. Epidermal innervation in racial and ethnic skin types was also assessed. No apparent difference in innervation was observed between European caucasian and Japanese/Chinese skin at the architectural or biochemical level, i.e. the presence, properties and biochemical content of fibres was similar in all cases tested.
Br J Dermatol 1997 Aug
PMID:The epidermal nerve fibre network: characterization of nerve fibres in human skin by confocal microscopy and assessment of racial variations. 929 61

Sodium-butyrate-pretreated and Con A-stimulated P815 mast cell line generated 3T3 fibroblast proliferating activity. This fibroblast stimulatory activity was partially abrogated by three different substance P antagonists such as spantide (NK1 antagonist), FK224 (NK1 and NK2 antagonist) or FK888 (NK1 antagonist) or anti-substance P antibody. In addition to P815 mastocytoma cell, IL3-dependent, bone marrow-derived mast cells also generated fibroblast proliferating activity which was also partially abrogated by substance P antagonists. Anti-fibrogenic cytokine antibodies also inhibited mast cell-derived fibroblast proliferating activity. Substance P or histamine augmented fibrogenic cytokine-induced fibroblast proliferation which indicates that mast cell-derived histamine or substance P play an important role in induction of tissue fibrosis in fibrosing diseases.
J Dermatol Sci 1997 Sep
PMID:Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis. 930 48

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.
Br J Dermatol 1997 Sep
PMID:The effects of topical doxepin on responses to histamine, substance P and prostaglandin E2 in human skin. 934 34

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.
Arch Dermatol Res 1997 Oct
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.
Br J Dermatol 1997 Dec
PMID:Skin, immunity and the nervous system. 947 Aug 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>