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

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.
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PMID:Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine. 618 98

Recent data have shown both synergistic and inhibitory effects between calcitonin gene-related peptide (CGRP) and substance P (SP) on inflammation and flare responses. The modulatory effects of CGRP on the itch, flare and weal responses following intracutaneous injections of SP and histamine were studied in 10 healthy volunteers. The only change in itch responsiveness observed was a significant prolongation of itch latency following SP when preceded 10 min earlier by a CGRP injection. No influence on flare and weal was observed.
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PMID:Influence of calcitonin gene-related peptide on histamine- and substance P-induced itch, flare and weal in humans. 750 47

We compared the behavioral effects of treatment with pruritogenic and algesiogenic agents in mice. The animals were given subcutaneous injections of pruritogenic agents, compound 48/80 (3-100 micrograms), substance P (10-300 micrograms) and histamine (3-300 micrograms), and algesiogenic agents, capsaicin (30 and 100 micrograms) and dilute formalin (5 mg of formaldehyde), into the rostral back, and scratching of the injected site by the hind paws was counted. Compound 48/80 and substance P dose dependently elicited the scratching behavior, but histamine, capsaicin and dilute formalin were without significant effects at the doses examined. These results suggest that compound 48/80- and substance P-induced scratching of the injected site is due to itch, but not to pain. The data did not provide support for the idea that histamine produces itch in the mouse.
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PMID:Scratching behavior induced by pruritogenic but not algesiogenic agents in mice. 753 79

Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.
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PMID:[Neurokinins and the skin]. 769 70

The etiology of atopic pruritus is unclear and seems mostly histamine-independent. In order to investigate non-mast cells as possible sources of pruritogenic agents, peripheral blood mononuclear cells from 12 atopic eczema patients and 12 controls were incubated in vitro for 24 h with phytohemagglutinin or concanavalin A (both at 10 micrograms/ml) or with medium alone, and each subject was tested with his own cell supernatants and lysates by prick testing and by application on tape-stripped skin. Histamine (0.1%) and substance P (500 microM) were tested in comparison, and reactions were observed for up to 24 h. Cell supernatants were also analysed for their contents of several cytokines. Lymphocyte cell extracts or supernatants failed to cause symptoms in controls but induced whealing in 6 and itching in 3 patients on prick testing within 5 min, lasting for 30 min in 2 patients and persisting for 6 h in 1 patient. Histamine caused itching in all controls and in 7 patients within 5 min on prick testing, with decreasing reactivity at later times. Substance P yielded results with lower values. With all three types of test reagents, fewer subjects reacted on tape stripped skin. High levels of interleukins 2 and 6, low levels of interferon and no detectable levels of interleukin 4 and tumour necrosis factor were measured in stimulated cell supernatants and extracts, with even lower levels in subjects exhibiting skin reactivity. These findings thus provide evidence that as yet unidentified mononuclear cell products may be involved in whealing and itching associated with atopic eczema.
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PMID:Pruritogenic effects of mitogen-stimulated peripheral blood mononuclear cells in atopic eczema. 865 Oct 16

Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients.
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PMID:Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. 873 Apr 31

Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes present in early stages of the disease. This prompted us to study the innervation of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive intestinal peptide were used for autonomic nerves. Sensory innervation was studied using antibodies to substance P and calcitonin gene-related peptide. Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies from affected (lower arm) and non-affected (upper back) sites on 10 patients with systemic sclerosis and from corresponding sites on 10 sex- and age-matched healthy controls were studied. Regional variations were found in the occurrence of peptidergic nerve fibers. In the patients the density of nerve fibers (measured semiquantitatively) stained by the panneuronal marker was lower in affected than in unaffected skin (p < 0.05). There were no significant differences in peptidergic innervation between patients and controls. However, there was a tendency to higher density of neuropeptide Y-positive nerve fibers in the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy controls.
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PMID:Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis. 874 Feb 66

Itching is the predominant symptom of skin disease but it is ill-understood and a challenge for future research. Even the major nerve pathways for itch, and its relationship to pain are debatable. In inflamed skin, histamine plays a major role and its mode of release from mast cells in, for example, chronic urticaria is now better appreciated. Tachykinins including substance P and cytokines including interleukin-2 are evidently important peripherally. Opioid mu-receptor-dependent processes activate inhibitory circuits in the central nervous system and regulate the extent of intensity and quality of perceived itch. It is proposed that stimulation of large areas of skin such as by scratching, generates inhibitory activity which suppresses itch excitation. Therapeutic intervention based upon understanding these regulatory processes is a real prospect.
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PMID:Pathophysiology of itching. 894 93

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.
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PMID:Neuropeptides in the skin of patients with atopic dermatitis. 885 37

Knowledge of biochemical and molecular events during burn wound healing may optimize treatment of patients with thermal injuries. Substance P (SP), a neuropeptide present in C fibers of the skin, has been implicated as a mediator of inflammation and wound healing. This neuropeptide induces vasodilitation and vascular permeability by stimulating endothelial cells to round up, vascular smooth cells to relax, and mast cells to release histamine. SP also induces cytokine release by macrophages and neutrophils. Because many of the functions of SP seemed relevant to wound repair in burns, we used immunocytochemistry to characterize SP+ nerve fibers in healing human burn wounds. Deep partial-thickness burns collected from 20 patients at the time of excision and grafting were formalin fixed, paraffin-embedded, sectioned, and labeled with a monoclonal antibody to SP with use of an immunoperoxidase technique. Our tissue samples included normal skin and 20 specimens from postburn days 2 through 49. In normal adult skin, SP+ nerve fibers surrounded vessels throughout the skin and extended from the papillary dermis into the epidermis. SP+ fibers were absent in early wound beds. SP immunostaining did occur in the advancing epidermis, endothelial cells, and mast cells. SP+ fibers could be identified in the deep dermis and subjacent to the advancing epithelium before the wound beds. Maximum numbers of SP+ fibers were present subjacent to the advancing epithelium at 2 weeks after burn injury. After 4 weeks, the distribution of SP+ fibers in reepithelialized areas was similar to that of normal skin. Our data corroborate published reports of SP+ fiber regeneration in guinea pig burns and correlates with clinical observations of pain and pruritus in patients with thermal injuries. The absence of SP+ fibers in the early wounds with SP immunostaining in the epidermis and extracellular matrix suggests that SP may be released from injured nerves and supports neurogenic mediation of inflammation and vasodilitation in early wound repair. Repopulation of the wound beds with SP+ fibers appeared to follow neovascularization originating in the deep reticular dermis and wound edge.
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PMID:Substance P has a role in neurogenic mediation of human burn wound healing. 888 61


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