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)

It is supposed that neuropeptides participate in the regulation of delayed-type hypersensitivity (DTH) reactions. However, their function in this kind of immune response is not known presently. Therefore, in vivo studies were initiated to test the effect on allergic (ACD) and irritant contact dermatitis (ICD) of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM), which are released from afferent neurons in the skin. Each neuropeptide was applied topically at the site of contact with the allergen (oxazolone) or irritant (croton oil) during the challenge and sensitization phase of contact dermatitis. The intensity of the inflammation was measured as an increase of ear-swelling response, which represents the degree of plasma extravasation in the early phase of inflammation. Neuropeptides alone led only to a distinct vasodilation. All three neuropeptides were equally able to increase allergic and irritant inflammation. Even minor irritant stimuli were enhanced. Beyond that, CGRP was able to boost sensitization, whereas SOM and SP did not show any effects on the sensitization process. The results presented demonstrate that neuropeptides increase plasma extravasation independent of the pathogenesis of inflammation and may act as priming substances for other mediators of increased vascular permeability. In addition, CGRP enhances the sensitization process.
J Invest Dermatol 1991 May
PMID:Neuropeptides enhance irritant and allergic contact dermatitis. 170 95

The role of substance P (SP) in allergic reactions of the skin was investigated. Spantide, a competitive inhibitor of SP, was injected intracutaneously into the volar aspect of the forearm prior to the following challenges: benzalkonium chloride (irritant delayed reaction), tuberculin (immunological delayed reaction), UVB irradiation, benzoic acid (non-immunological contact urticaria), different food allergens and latex (in patients with immunological contact urticaria). Only the immunological reactions of contact urticaria and the reaction to tuberculin were suppressed by the SP antagonist, indicating that SP is involved in their pathogenesis.
Br J Dermatol 1991 Apr
PMID:Substance P antagonist inhibits immediate and delayed type cutaneous hypersensitivity reactions. 172 11

In early phases of cutaneous inflammation, connective tissue mast cell degranulation is associated with apparent secretion and externalization of immunoreactive chymotryptic serine proteinase. To determine whether this event is associated with structural evidence of granule externalization, we studied the sequential evolution of IgE-mediated hypersensitivity in vivo, as well as mast cell degranulation provoked by a variety of stimuli in cultured explants of human skin. By 1 min after intradermal antigen challenge with ragweed extract, mast cell degranulation was associated with apparent extrusion of intragranule constituents into the pericellular connective tissue. Similar features typified cultured skin explants exposed for 45 min to anti-IgE and other mast cell secretagogues (morphine sulfate, calcium ionophore A23187, compound 48/80, and substance P). Once externalized, granule constituents could be identified within the dermal matrix by their rounded contour and structural similarity to solubilized granule matrices remaining within actively secreting cells. These data indicate that externalization of connective tissue mast cell granule contents occurs early after secretagogue exposure, potentially accounting for infrequent documentation of this event in naturally occurring dermatoses. The ability to recognize externalized granule products at a morphologic level should facilitate the understanding of interactions between mast cell-derived mediators and target structures of the dermal microvasculature.
J Invest Dermatol 1991 Jun
PMID:Extracellular localization of human connective tissue mast cell granule contents. 171 Jun 37

The neuropeptides vasoactive intestinal polypeptide (VIP), substance P and somatostatin were studied in skin biopsies from patients with eczema, psoriasis and axillary hyperhidrosis. VIP concentrations were elevated in skin affected by eczema and psoriasis, whereas substance P and somatostatin levels did not differ from controls. There was a higher concentration of VIP, but not of substance P or somatostatin, in normal axillary skin when compared to adjacent trunk skin, with abundant VIP-containing fibres surrounding eccrine sweat glands. The VIP concentration was unchanged in skin affected by axillary hyperhidrosis. VIP may increase local blood flow in eczema and psoriasis, but does not appear to play a role in axillary hyperhidrosis.
Br J Dermatol 1991 Jun
PMID:Neuropeptides in skin disease: increased VIP in eczema and psoriasis but not axillary hyperhidrosis. 171 21

The action of histamine on human dermal microvascular endothelial cells and modulation of its effects by the cytokine interleukin-1 and the vasoactive neuropeptide substance P have been investigated. Histamine (10(-6)-10(-3) M) induces release of prostaglandin E2 in a concentration- and time-dependent manner. Prostaglandin E2 release is facilitated principally by histamine H1 receptors as the H1 receptor antagonist pyrilamine attenuates prostaglandin E2 release whereas the H2 receptor antagonist cimetidine only slightly reduces release. In contrast to other cells, the histamine/receptor interaction is not associated with increased intracellular accumulation of the cyclic nucleotides, cyclic AMP, or cyclic GMP. Interleukin-1 induces a concentration-dependent release of prostaglandin E2 following 24 h incubation. However, substance P does not increase release of prostaglandin E2 above baseline. In cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h prior to stimulation with histamine (10(-5)-10(-3) M) for 30 min, there is a significant potentiation of histamine-induced release of prostaglandin E2 (p less than 0.05). Using a solubilized cell sonicate prepared from human dermal microvascular endothelial cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h, conversion of exogenous arachidonic acid into prostaglandin E2 increased by 60.19 +/- 18.28%. Cycloheximide partially reduces the increased conversion but completely blocks interleukin-1-induced release of prostaglandin E2 from intact cells. Substance P does not potentiate histamine-induced release of prostaglandin E2 or increase arachidonic acid conversion. These results demonstrate that human dermal microvascular endothelial cells are responsive to histamine and that interleukin-1, but not substance P, can potentiate histamine-induced release of prostaglandin E2. Interleukin-1 appears to act, at least in part, by regulating the availability of free arachidonic acid. Interactions between histamine and interleukin-1 may be important in the modulation of inflammatory reactions in skin.
J Invest Dermatol 1991 Nov
PMID:Responses of human dermal microvascular endothelial cells to histamine and their modulation by interleukin 1 and substance P. 171 8

Pruritus is a significant problem for many patients undergoing long-term hemodialysis. Topical capsaicin depletes and prevents the reaccumulation of substance P in peripheral sensory neurons. Substance P functions in the transmission of pain and probably itch sensations. An open-label, uncontrolled trial and a double-blind, vehicle-controlled trial were conducted to evaluate the efficacy and safety of capsaicin 0.025% cream in the treatment of localized areas of pruritus in patients undergoing long-term hemodialysis. Eight of nine evaluable patients in the open-label trial reported marked relief or complete resolution of itching during the study period, and two of five evaluable patients in the double-blind trial reported complete resolution of itching in the capsaicin-treated arm with no or minimal improvement in the vehicle-treated arm. Twelve patients in the open-label trial and two in the double-blind trial were unevaluable. No serious treatment-related adverse reactions occurred.
J Am Acad Dermatol 1992 Jan
PMID:Topical capsaicin for treatment of hemodialysis-related pruritus. 173 43

Notalgia paresthetica is a sensory neuropathy characterized by infrascapular pruritus, burning pain, hyperalgesia, or tenderness. To assess whether the symptoms may be caused by alterations in the cutaneous innervation, skin from the affected area of patients (n = 5) was compared with controls (n = 10) comprising the contralateral unaffected area from the same patients and site-matched biopsies of normals, using immunohistochemistry. Frozen sections were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide with tyrosine, and to the general neural marker PGP 9.5 and the glial marker S-100 to show the overall innervation and glial cells, respectively. No discernible change in the distribution of neuropeptide-immunoreactive axons was found, but all of the specimens from the affected areas had a significant increase in the number of intradermal PGP 9.5-immunoreactive nerve fibers compared with unaffected areas from the same patients and normal controls. Epidermal dendritic cells immunoreactive for S-100, possibly Langerhans cells, were substantially increased. It is concluded that there is an increase in the sensory epidermal innervation in the affected skin areas in notalgia paresthetica, which could contribute to the symptoms, and that neural immunohistochemistry of skin biopsies could be helpful in the diagnosis of the disease.
J Invest Dermatol 1991 Sep
PMID:Symptoms of notalgia paresthetica may be explained by increased dermal innervation. 183 66

Differentiation of the hair was examined in the head skin of rat embryos aged from days 12.5 to 18.5 of gestation. In 12.5-day-old embryos, the skin consisted of single layered epidermis and underlying loose connective tissue. On day 17.5 of gestation, the epidermis appeared to have a two or three layered epithelium, and the subepidermal connective tissue gave rise to an overlying dense tissue, into which blood capillaries arose from the deeper layer. The epidermis showed partial thickenings, where basal cells were arranged perpendicular to the surface of the epidermis. Beneath the epidermal thickenings, a number of connective tissue cells appeared to have accumulated and occasionally were accompanied by blood capillaries. In sequential development of the skin, the thickenings protruded as cords to the underlying dermal tissue and formed hair follicles covered with a connective tissue sheath. Skin obtained from 12.5-day-old embryos was transplanted singly or with cerebral cortex into the third ventricle of adult male rats. Thirty days after the transplantation, hairs and sebaceous glands had developed from the grafted skin. Hair growth tended to be more prominent in the cotransplanted skin grafts. However, no nerve fibers immunoreactive for substance P or calcitonin gene-related peptide (CGRP) were found in the grafted skin, although these fibers appeared in the dermis at the end of gestation in vivo. These results showed that the skin of 12.5-day-old embryos was able to induce hair growth in the third ventricle without accompanying peripheral neuronal fibers or blood capillaries, although the effects of connective tissue cells could not be ruled out.
J Dermatol 1991 May
PMID:Development of the hair in the rat: in vivo and in transplanted tissue. 193 53

The pathophysiology of Raynaud's phenomenon is not well defined, but active cutaneous microvascular vasoconstriction and emptying must occur to account for the pallor and are reasons for studying the microvasculature. It has been proposed that there may be a defect in a local histamine vasodilator mechanism. The role of the peptidergic nervous system in Raynaud's phenomenon has not been previously investigated. To study the histaminergic and peptidergic axes in Raynaud's phenomenon, we measured the cutaneous microvascular responses of patients with Raynaud's phenomenon to digital intradermal injections of saline, histamine, the histamine-releasing agent, compound 48/80, substance P, and calcitonin gene-related peptide. We compared these results with those obtained in normal subjects. Intradermal cutaneous microvascular blood flow responses were quantified by planimetry and laser Doppler flowmetry. The results show: a) that in primary Raynaud's phenomenon there is no evidence of local deficiency in histamine release or insensitivity to histamine in the cutaneous microvasculature; and b) that patients with Raynaud's phenomenon react normally to the neuropeptides calcitonin gene-related peptide and substance P, providing a rationale for treating Raynaud's phenomenon with vasoactive peptides.
J Invest Dermatol 1991 Mar
PMID:Digital cutaneous vascular responses to histamine and neuropeptides in Raynaud's phenomenon. 200 51

The present study examines the presence of neuropeptides in the skin and plasma of patients with psoriasis using the techniques of immunocytochemistry and radioimmunoassay. Immunocytochemistry failed to demonstrate differences in the pattern of neuropeptide innervation in psoriatic lesional skin when compared to normal skin. However, radioimmunoassay of skin biopsy extracts, both substance P and vasoactive intestinal polypeptide, were significantly elevated in psoriatic lesional skin when compared with both psoriatic non-lesional and normal control skin (p less than 0.001). There was no significant difference between the plasma levels of neuropeptides in psoriatic patients compared to those of control subjects, and no significant correlation among the plasma levels of neuropeptides with the surface area of involvement with psoriasis. The finding of elevated levels of substance P and vasoactive intestinal polypeptide in lesional psoriatic skin suggests that these peptides may be involved in the pathogenesis or maintenance of the psoriatic skin lesion and the development of safe and stable antagonists of these neuropeptides may have applications in the treatment of psoriasis.
J Invest Dermatol 1991 Apr
PMID:Neuropeptides in psoriasis: an immunocytochemical and radioimmunoassay study. 200 81


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