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)

An enzyme with the specificity of a prolyl endopeptidase was purified approximately 329-fold from rat skin. The enzyme has a molecular weight of 70,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a pH optimum of 5.8 as checked with 7-(Succinyl-Gly-Pro)-4- methylcoumarinamide (Suc-Gly-Pro-MCA) as the substrate. The optimal temperature for the enzyme activity was 40 degrees C. The Km and Vmax values for Suc-Gly-Pro-MCA were 0.7 mM and 68 nmol/min per mg protein, respectively. The enzyme activity was markedly inhibited by diisopropyl fluorophosphate, p-chloromercuribenzoic acid, N-ethylmaleimide, Zn2+ and Cu2+, while it was partially inhibited by phenylmethanesulphonyl fluoride. The purified enzyme was shown to release the N-terminal tetrapeptide, Arg-Pro-Lys-Pro, from substance P producing the C-terminal heptapeptide, Gln-Gln-Phe-Phe-Gly-Met- CONH2. In the skin, this enzyme might be related to the inactivation of substance P.
J Dermatol Sci 1993 Oct
PMID:Purification and characterization of prolyl endopeptidase from rat skin. 750 52

The complement peptides C3a and C5a have been shown previously to release histamine from human basophils but not human lung mast cells. As skin mast cells differ from those of the lung in both immunocytochemical and functional properties, we examined the ability of these anaphylatoxins to release preformed and newly generated mediators from human dispersed skin mast cells. In concentration-response studies, both C3a and C5a released histamine in a concentration related manner with C5a being 40-50 times more potent. However, the extent of histamine, 15-20%, was considerably less than that released from basophils. This was not due to catabolism of the peptides by mast cell proteases, mast cell supernatants that contained C5a being effective in releasing basophil histamine. Removal of the C-terminal arginine from C3a and C5a abolished their activity on skin mast cells. In time-course studies, histamine release induced by C3a and C5a was complete within 15 seconds. Complement-induced histamine release is a non-cytotoxic process as evidenced by 2-deoxy-D-glucose and antimycin A, inhibitors of glycolysis and oxidative phosphorylation, respectively. In contrast to IgE-dependent stimulation, anaphylatoxin-induced histamine release from human skin mast cells is independent of extracellular calcium. Both C3a and C5a at concentrations that induced 10-16% net histamine release caused a negligible release of the newly generated mediator, PGD2. The results suggest that C3a and C5a stimulate human skin mast cells in a manner similar to substance P and related basic secretagogues. However, the activation site for C3a and C5a appears to be different to that for substance P as the substance P antagonist (D-Pro4, D-Trp7,9,10) SP4-11 inhibited histamine release stimulated by substance P but not that induced by C3a and C5a.
J Invest Dermatol 1994 May
PMID:Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. 751 41

Specimens of hypertrophic scar tissue (n = 9), non-hypertrophic, flat scar tissue (n = 5) and control skin (n = 3) were obtained from eight adult females (aged 22-56) and three adult males (aged 22-59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamine beta-hydroxylase. The non-hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue. The normal skin contained all the neuropeptides studied, except somatostatin-, and dopamine beta-hydroxylase-immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine beta-hydroxylase-containing nerves were found within sweat glands. In patients with flat, non-hypertrophic scar tissue, neuropeptides and dopamine beta-hydroxylase-containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-, calcitonin gene-related peptide- and dopamine beta-hydroxylase-immunoreactive nerves was greater in the dermis when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Br J Dermatol 1994 Apr
PMID:Neuropeptide-containing nerves in painful hypertrophic human scar tissue. 751 32

Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca2+) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca(2+)-sensitive dye, Fura 2-AM. Treatment of normal human epidermal keratinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca2+. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca2+ signal.
Exp Dermatol 1994 Feb
PMID:Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes. 752 Mar 37

Neuropeptide and neuronal marker immunoreactivity was studied in skin biopsies from lesional and marginal areas in 12 patients with vitiligo, and in seven normal controls. The vitiligo was active in seven, static in two, and of unknown activity in three. Antibodies against general neuronal marker PGP 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY), were used. The epidermis, dermo-epidermal junction, papillary and reticular dermis, and appendages, were assessed semiquantitatively for reactivity with each antibody. Staining with PGP 9.5 in the upper dermis was assessed quantitatively by image analysis. An increase in reactivity against NPY antibody was seen in five of 10 cases (three with active vitiligo) in the marginal areas, and in three of 12 subjects (all with active vitiligo) in the lesional vitiligo areas. VIP antibody reactivity showed a minimal increase in the marginal and lesional vitiligo areas (in two cases each, both of whom had active vitiligo). SP and CGRP reactivities did not differ from normal. PGP 9.5 staining was minimally increased at the dermo-epidermal junction and lower Malpighian layer in biopsies from marginal areas in three of 10 subjects (all with active vitiligo). Quantitative analysis of PGP 9.5 reactivity in the upper dermis showed no difference between vitiligo and normal biopsies. These findings support the concept of neuronal or neuropeptide involvement in vitiligo, and in particular suggest that NPY may have a role in the pathogenesis of the disease.
Br J Dermatol 1994 Aug
PMID:Neuropeptide and neuronal marker studies in vitiligo. 752 12

The effects of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) on leukocyte infiltration during allergic contact dermatitis (ACD) in mice were studied. Concomitant topical application of SP or CGRP with the allergen oxazolone resulted in enhanced leukocyte recruitment at the sites of challenge. Immunohistochemical studies revealed that the numbers of T-helper (L3T4+) and cytotoxic (Lyt-2) lymphocytes and infiltrating macrophages (BM8+) were increased. In addition, ICAM-1 and MHC class II molecule expression by these cells was enhanced after neuropeptide application. Analysis by confocal laser scanning microscopy revealed an increase in the immunoreactivity for SP and CGRP in nerve fibres during the course of ACD. Flow cytometry studies showed that SP and CGRP did not upregulate expression of the adhesion molecules ICAM-1 and VCAM-1 by murine endothelial cell lines in vitro. This suggests that increased infiltration of leukocytes during ACD is not a consequence of direct neuropeptide-promoted upregulation of endothelial adhesion molecules in vivo. In conclusion, our observations provide evidence for a modulatory role of neuropeptides in the pathogenesis of ACD.
Arch Dermatol Res 1994
PMID:Substance P and calcitonin gene-related peptide modulate leukocyte infiltration to mouse skin during allergic contact dermatitis. 752 6

In this study radioimmunoassay was used to determine neuropeptide levels in extracts from 17 differing anatomical regions of human skin. Marked regional variations of neuropeptide content for human skin were found and these variations are likely to reflect true physiological functions for the neuropeptides studied. In general the tachykinins, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were found in highest concentrations in regions of skin with the greatest tactile sensation. By contrast, highest concentrations of vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) were found in axillary skin, where they probably play a part in axillary eccrine sweat production. Neurotensin was not found in any of the skin areas sampled, suggesting that it is relatively unimportant in human physiological skin control. Reverse-phase high-performance liquid chromatography (rpHPLC) was used to verify the results of radioimmunoassay. Both SP and NKA occurred in several regions in both their reduced and oxidized forms, as well as displaying molecular heterogeneity. CGRP occurred as one molecular species, this being alpha-CGRP, suggesting that this is the predominant molecular form in human skin. Likewise, both VIP and PHM displayed molecular homogeneity in the regions investigated by rpHPLC.
Clin Exp Dermatol 1994 Nov
PMID:The regional distribution of neuropeptides in human skin as assessed by radioimmunoassay and high-performance liquid chromatography. 753 21

The distribution of binding sites for NTE-biotinyl-[Arg3]-substance P (SPB) was demonstrated in neonatal foreskin using a conjugate of streptavidin with horseradish peroxidase. The observed binding is reversible, and may be abrogated by either the non-peptide substance P receptor antagonist, CP-96,345, or by unlabelled substance P. The generalized epidermal distribution and focal dermal localization of SPB binding suggest that although NK-1 receptors are abundant in human neonatal foreskin, neuromodulatory mechanisms may play a significant role in epidermal physiology.
Br J Dermatol 1995 Jan
PMID:Substance P binding in normal neonatal foreskin. 753 77

The mitogenic effect of the neuropeptide substance P and bombesin was investigated in normal human keratinocytes in serum-free culture, both with and without the presence of epidermal growth factor (EGF). Although both neuropeptides induced a small increase in cell numbers in the presence of EGF, the response was much greater in its absence, and cell numbers increased to 200% of controls at 5 days. Changes in intracellular free calcium are frequently seen following mitogenic stimulation of cells, and this phenomenon was studied in individual keratinocytes. Epidermal growth factor (10 ng/ml) induced calcium transients in 57% (n = 21) of cells. The mean intracellular free calcium was 97 +/- 11 nM (mean +/- SEM) in quiescent cells, and the calcium transients reached approximately 250 nM for 3-4 min. In the presence of EGF, calcium transients were never observed with the addition of either substance P or bombesin. For EGF-deprived cultures, 20% of keratinocytes (n = 10) showed a large calcium transient following the addition of 500 nM bombesin, and 63% (n = 12) of cells gave calcium transients following the addition of 700 nM of substance P. Studies in calcium-free medium, and following depletion of intracellular calcium stores with thapsigargin, showed that all of the calcium transients were dependent on the presence of intracellular stores, but also partially mediated by an influx of extracellular calcium. These studies demonstrate the mitogenic effect of substance P and bombesin on human keratinocytes in the absence of EGF. The ability of the neuropeptides to increase keratinocyte growth in culture suggests a possible in wound healing.
Br J Dermatol 1995 Jun
PMID:Intracellular calcium as a second messenger following growth stimulation of human keratinocytes. 754 93

Sunburned skin is characterized by expanded numbers of macrophages (ultraviolet [UV]-MPH), and these UV-MPH differ from Langerhans cells (LC) in their abilities to initiate T-cell-mediated immune reactions. UV-MPH and LC may themselves be differentially responsive to the surrounding milieu, which may in turn modulate their immunoregulatory activity. We asked whether immunologic signal responsiveness, as assessed by cytosolic calcium mobilization, differed among normal human LC, UV-MPH, and normal blood monocytes. LC from normal skin and UV-MPH from UV-exposed skin were distinguished from keratinocytes in epidermal cell suspensions by labeling with anti-HLA-DR. Intracellular calcium content was monitored in real time with the calcium indicator, indo-1, after cross-linking Fc gamma RI, Fc gamma RII, CD11b, CD11c, or CD18 molecules, or addition of interleukin-1 alpha, IL-1 beta, interferon-gamma, bradykinin, substance P, or FMLP. Using flow cytometric analysis of cell suspensions, UV-MPH and blood monocytes were triggered by cross-linking Fc gamma RII (flux of 6.05 and 12.2, respectively). UV-MPH could also be triggered by Fc gamma RI crosslinking and FMLP (flux of 6.41 and 15.54, respectively). By contrast, none of these inflammatory stimuli could cause cytosolic calcium mobilization in normal LC (Flux of -0.2 by FcRII, and 0.18 by FMLP). Because LC calcium flux may be dependent upon extracellular attachments, LC were anchored onto fibronectin-coated coverslips and then their Fc gamma RII was crosslinked in a continuous flow chamber. However, image analysis also failed to detect calcium flux. Neither population responded to interleukin-1, interferon-gamma, bradykinin, substance P, or beta 2 integrin crosslinking. These results indicate that blood monocytes and infiltrating macrophages differ substantially from LC in their responses to immune complexes and chemoattractants. Differential responsiveness to the inflammatory milieu may influence the antigen presenting or effector capabilities of these populations.
J Invest Dermatol 1995 Sep
PMID:Differential extracellular signaling via Fc gamma R and FMLP in functionally distinct antigen-presenting cell subsets: ultraviolet-induced epidermal macrophages versus Langerhans cells. 766 17


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