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)

Pruritus, whealing and axon-reflex erythema appeared in human skin after intradermal injection of (i) several peptides with a putative transmitter function, i.e. vasoactive intestinal polypeptide (VIP) (10(-7)--10(-4) M), [Gln4]-neurotensin (10(-7)--10(-4) M), neurotensin (10(-5)--10(-4) M) and secretin (10(-5)--10(-4) M), which were compared with substance P (10(-7)--10(-5) M) previously shown to be one of the most potent histamine liberators when administered intradermally in humans; (ii) the basic polypeptide protamine (10(-7)--10(-4) M); and (iii) histamine (0.3-10 micrograms/ml) and the histamine liberator compound 48/80 (0.3-10 micrograms/ml). The reactions were inhibited in a dose-related manner by the antihistamine mepyramine, indicating that the peptide-induced responses were mediated by released histamine. This was further confirmed by the histamine release observed when the peptides were incubated with rat peritoneal mast cells. In human skin, VIP was more potent than the other neuropeptides and had roughly the same potency as substance P. The two adjacent basic amino-acid residues and the amide substitution of the terminal C-group of VIP, in addition to its strong net basic charge, may explain its potency as a histamine releaser.
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PMID:Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters. 616 9

The mechanism of cutaneous inflammation caused by substance P in human skin was assessed in five subjects receiving i.d. injections (5-405 pmol) at pH 7.2 as compared to histamine (0.08-1.6 nmol), compound 48/80 (100 ng) and solvent control. Both substance P and histamine produced sigmoid dose-response curves for the following parameters: 1 min and 5 min planimetrically measured areas of erythema, and mean diameter of weal. Substance P pretreatment induced tachyphylaxis, as assessed by standard methods with adequate controls, to both histamine and to substance P and vice versa. Erythema following substance P i.d. was not blocked by a constricting band. Diphenhydramine, and to a lesser extent doxantrazole, (but not cimetidine or indomethacin) when assessed as inhibitors after oral pretreatment, did shift dose response curves for histamine and substance P to the right. Light and electron microscopic assessment of mast cells was compared in substance P and solvent control injected human skin. These results support a possible role for substance P in cutaneous inflammation acting either directly or via histamine release from mast cells.
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PMID:Vascular responses of human skin to injection of substance P and mechanism of action. 618 19

Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) coexist in nerve fibres in the skin. CGRP causes erythema upon intracutaneous injection. The erythema is independent of axon reflexes and release of mast cell histamine. SP is known to produce a flare reaction that is dependent on axon reflexes and release of mast cell histamine. The flare reaction to NKA is known to depend predominantly on axon reflexes. The purpose of the present study was to investigate possible cooperation between SP and CGRP. SP was found to shorten the duration of the reddening induced by CGRP, injected concomitantly. NKA did not shorten the duration of the CGRP response. Local elimination of mast cells in the skin by treatment with compound 48/80 had the effect that SP lost its ability to shorten CGRP-evoked erythema. These observations support the suggestion that an SP-evoked release of proteolytic enzymes from mast cells could lead to accelerated degradation of CGRP.
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PMID:Interaction between tachykinins and CGRP in human skin. 750 67

1. We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2. Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3. Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 micrograms per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine H1 and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca(2+)-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema. 4. Phosphoramidon (50 micrograms kg-1, i.v.), an endopeptidase inhibitor, markedly (P < 0.001) enhanced only capsaicin-induced ear oedema, but bestatin (0.5 mg kg-1, i.v.), an aminopeptidase, failed to enhance oedema formation. 5. Neuropeptides (1-100 pmol per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicin-sensitive neurones, caused ear oedema by intradermal injection. Furthermore, a synergistic effect of CGRP (10 fmol per site) and SP (10 pmol per site) on oedema formation was observed. 6. The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-1, p.o.), a histamine H, and 5-HT antagonist, was administered before injection. In contrast, nifedipine (50 mg kg-1, p.o.), a Ca2+-channel blocker, and indomethacin(10 mg kg-1, p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on neuropeptide induced oedema.7. These results suggest that the mechanism of capsaicin-induced ear oedema is different from that of AA-induced oedema and suggest that the development of capsaicin-induced ear oedema is primarily mediated by neuropeptides. The neuropeptides released after activation of sensory nerves cause an increase of vascular permeability by interactions with endothelial cells and by histamine (and 5-HT)release from mast cells.
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PMID:Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema. 750 28

Experimental inflammation produced by an intraplantar injection of complete Freund's adjuvant results in local sensory hypersensitivity and up-regulates the neuropeptides substance P and calcitonin gene related peptide in the primary sensory neurons innervating the inflamed tissue. The inflammation also elevates nerve growth factor levels in the skin. Systemic administration of anti-NGF neutralizing antibodies prevent the behavioral sensitivity, the up-regulation of neuropeptides and the inflammation-induced expression of the immediate early gene c-fos in dorsal horn neurons, without modifying swelling and erythema. Elevation of the neurotrophin NGF in the periphery is a major contributor, therefore, of inflammatory pain.
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PMID:Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. 753 Mar 42

The possible involvement of substance P released from primary afferents in rat skin was investigated in cutaneous inflammation following ultraviolet (UV) irradiation. Recordings from c-fibres innervating the UV-exposed hindpaw skin showed long-lasting low-frequency (0.8-1.25 Hz) spontaneous activity. Spontaneously active c-fibres increased to constitute 35.3% of the total population 72 h after UV exposure. Immunohistochemical analysis of substance P-containing nerve fibres in hindpaw skin revealed a significant increase in substance P immunoreactivity 24 h after UV irradiation. Average length of substance P-immunolabelled nerve fibres was about two times higher in UV-exposed compared to control skin. UV-induced oedema was investigated in rat ears using an ear-swelling test. Intradermal injection of either peptide (Spantide) or nonpeptide (CP-96,345) substance P antagonists and epicutaneous application of CP-96,345 reduced UV-induced oedema significantly in the late phase of sunburn (> 12 h after UV exposure). The UV-induced increase in skin blood flow was investigated in hindpaw skin up to 72 h by the laser Doppler technique. Epicutaneous application of CP-96,345 reduced erythema significantly between 12 and 72 h after UV exposure. Thus, our findings suggest the involvement of neurogenic substance P as a proinflammatory mediator in the late phase of UV-induced cutaneous inflammation in rats.
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PMID:Involvement of substance P in ultraviolet irradiation-induced inflammation in rat skin. 755 Nov 78

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

For investigation of a possible relationship between cutaneous and bronchial hyperreactivity, 74 subjects were grouped according to the presence (n = 33) or absence (n = 41) of urticarial dermographism after application of a standardized shearing pressure with a dermographometer (12.7 x 10(5) Pa). the two groups did not differ in age, sex, smoking habits, presence of urticaria and atopy, or serum IgE levels. Erythema of the dermographic test sites was always significantly greater (P < 0.001) in the group with urticarial dermographism at 2, 4, and 8 min, and cutaneous reactivity with titrated prick tests was significantly increased in this group with low concentrations of histamine, 0.01% and substance P (0.25 mM) (P < 0.05). After bronchial provocation with acetylcholine, 51 of the 74 subjects, 25 with and 26 without urticarial dermographism, exhibited bronchial hyperreactivity. However, significantly more subjects with urticarial dermographism had an increase in airway resistance and a decrease in specific airway conductance (P < 0.05). In the subgroup (n = 9) of subjects with symptomatic urticarial dermographism (urticaria factitia), these differences were even more significant (P < 0.001). These subjects also had larger skin test reactions and significantly higher IgE levels (P < 0.01). Thus, the present data show an association, which may be based on common mechanisms of allergic inflammation, between cutaneous and bronchial hyperreactivity.
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PMID:Dermal and bronchial hyperreactivity in urticarial dermographism and urticaria factitia. 878 71

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

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.
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PMID:Effect of UVB 311 nm irradiation on normal human skin. 937 27


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