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 aim of the present study was to extend our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic, and that substance P mediates the inflammation. For this purpose, the pattern of neurofilament-positive sensory nerve fibers was studied and the lengths and substance P content of these fibers measured morphometrically in dermal and epidermal compartments of the psoriatic lesion, psoriatic but lesion-free skin, and control skin. The epidermis and dermis of the psoriatic lesions were significantly more densely innervated with neurofilament-positive fibers than either lesion-free psoriatic or control skin. Although substance P is known to be rapidly degraded in tissues, and its actual concentrations in the sections were unknown, there was an increase in substance P containing nerves in the psoriatic lesion, the increase being significant in the epidermal nerve fibers. No significant differences in the measured parameters were obtained between lesion-free psoriatic and control skin. These results indicate that there is an altered pattern of sensory nerves in a psoriatic plaque and that substance P may be an important mediator in the inflammatory processes that contribute either to the initiation or maintenance of a psoriatic lesion.
J Invest Dermatol 1989 Jan
PMID:Quantification of cutaneous sensory nerves and their substance P content in psoriasis. 279 54

Eight patients with intensely pruritic lesions of chronic idiopathic prurigo nodularis and three patients with neurodermatitis circumscripta were investigated using the indirect immunofluorescence method. Results showed similarities in epidermal hyperplasia but not in nerve proliferation and neuropeptide immunoreactivity. Increased numbers of calcitonin gene-related peptide (CGRP) and substance P immunoreactive nerve fibre bundles were detected in specimens taken from prurigo nodularis lesions, but no increased immunoreactivity could be seen in specimens taken from patients having neurodermatitis circumscripta compared to normal skin. The neuropeptides, CGRP and substance P, may be responsible for the intense itching of prurigo nodularis lesions.
Br J Dermatol 1989 May
PMID:Calcitonin gene-related peptide immunoreactivity in prurigo nodularis: a comparative study with neurodermatitis circumscripta. 247 15

Mast cells (MC) are widely distributed throughout different organs with a relative predilection for potential portals of entry into the host. In tissues, MC are generally concentrated around small blood vessels and lymphatics, as well as nerves and glandular tissue. This close association with vascular structures suggests an important interaction between MC and endothelial cells (EC). Tissue MC are known to generate and release a number of mediators including histamine, prostaglandin D2, and leukotrienes that induce vasodilatation and increased vascular permeability. These MC-mediated effects on vessels may enhance responses to tissue injury or infection by facilitating the deposition of plasma components and inflammatory cells into involved sites. Important interactions between MC, EC, and peripheral nerves also occur. MC-derived histamine and possibly other mediators induce axon reflexes in unmyelinated sensory nerves leading to the release of neurotransmitters such as substance P, calcitonin gene-related peptide, and adenine nucleotides. These neurotransmitters exert direct effects on blood vessels, and in some instances, may act as MC stimulators. In vitro studies indicate that MC also affect EC growth and new blood vessel formation. Mast cell-derived heparin has been implicated as an important cofactor in tumor-induced angiogenesis, whereas histamine has been reported to augment human dermal EC growth in culture. The recent identification of a tumor necrosis factor-like peptide in MC and the reported cytostatic effects of TNF on EC suggest that MC may inhibit the proliferation of these cells under certain conditions. Taken together, these observations indicate that the interactions between MC and EC are important in both physiologic and pathologic events.
J Invest Dermatol 1989 Aug
PMID:The interaction between mast cells and endothelial cells. 256 4

Adults with atopic dermatitis (AD), with respiratory atopy only and healthy non-atopic controls were given intradermal injections of substance P (SP), neurokinin A (NKA), neurotensin (NT), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and histamine into the normal-appearing skin on the back. The weal and flare responses were evaluated after 3, 5 and 15 min and the areas calculated using an automatic image analyser. With the three different concentrations used (1, 3 and 30 pmols) a statistically significant (P less than 0.05) reduction in both the weal and flare response to SP, NKA, NT and histamine and a reduced flare to CGRP was observed only in AD patients. Among those with AD there was no uniformity of response to the individual neuropeptide and in general the more severely affected showed a lower reactivity. Dose-response relationships were evaluated for SP and NT (10-320 pmols) in AD and healthy controls. In AD dose-response curves and time-course relationships were similar to controls, but at significantly reduced levels. The itch response to the neuropeptides and histamine was not different in atopics and controls. We suggest that this hyporesponsiveness in AD is the result of natural tachyphylaxis of the target structures (mast cells and blood vessels) and possibly due to a higher availability of neuropeptides in the skin or to a primary abnormal sensitivity of the blood vessels and mast cells to these peptides.
Br J Dermatol 1989 Dec
PMID:Skin reactivity to neuropeptides in atopic dermatitis. 261 Nov 20

Several non-opioid regulatory peptides have been described in normal human skin localized both in neural fibres and in cellular elements. These include substance P, neurokinin A, neurotensin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine methionine, neuropeptide Y, somatostatin, galanin and atrial natriuretic peptide. In the present review the morphological aspects and distribution of peptidergic nerves in normal human skin are presented. The main functional roles on nociception, pruritus, cutaneous blood flow and sweat production are discussed in regard to neuropeptides. The relationships between neuropeptides, mast-cells and neurogenic inflammation are discussed in detail. Pathological conditions are reported in which an alteration in the peptidergic control might be of importance in their pathogenesis. Some working hypothesis are discussed.
G Ital Dermatol Venereol 1989 Apr
PMID:[Neuropeptides and the skin: morphological, functional and physiopathological aspects]. 268 Sep 14

Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.
J Am Acad Dermatol 1987 Jul
PMID:Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study. 361 58

Topical application of capsaicin to human skin produced an initial burning erythematous reaction which diminished over 24 hr leaving the skin unresponsive to histamine-induced axon reflex vasodilatation without altering sensitivity to pain, touch and temperature. Depletion of substance P from local sensory nerve terminals is suggested as a possible explanation for this capsaicin effect.
J Invest Dermatol 1981 May
PMID:Inhibition of axon reflex vasodilatation by topically applied capsaicin. 616 37

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.
Arch Dermatol Res 1982
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

The regeneration of substance P (SP)-containing nerve fibers in the process of burn wound healing in the guinea pig skin has been studied by immunohistochemistry. SP-like immunoreactivity, which was specifically localized in neural elements of intact skin, was found to disappear in the burn wound including its margin on day 2 post burn. The SP-containing nerve fibers were first detected in periods later than day 2 post burn, and the regeneration seemed to occur in association with regeneration of blood vessels at the wound margins. These nerve fibers gradually increased in number and acquired maximum density on day 14 post burn. In addition, such renewed fibers showed sprouting to form a dense network, which has never been observed in intact skin, in the upper granulation tissue just beneath the regrowing epidermis. Following that peak period, the density of the fibers gradually decreased to less than that of controls. The characteristic process of regeneration of SP-containing nerve fibers, having a peak period of fiber density at least in burn wound healing, appeared similar to that of the regeneration of sympathetic catecholaminergic nerve fibers reported previously.
J Invest Dermatol 1984 Sep
PMID:The regeneration of substance P-containing nerve fibers in the process of burn wound healing in the guinea pig skin. 620 67

The increase in vascular permeability in small blood vessels of rat skin induced by antidromic stimulation of sensory roots, nerves, or single identified polymodal nociceptive fibres or by intra-arterial injection of Substance P, has been examined by light and electron microscopy. The effects of local application of capsaicin (a Substance P-depleting agent) to both skin and muscle have also been studied. Nerve stimulation and Substance P induce leakage of a venular pattern similar to that caused by known permeability factors. However, capsaicin causes leakage from both venules and capillaries in a pattern more characteristic of direct endothelial injury. It is suggested that neurogenic leakage may be mediated by local liberation of Substance P, but caution is necessary in interpreting experiments involving the use of capsaicin because of its local toxic effects.
Br J Dermatol 1984 Nov
PMID:The role of substance P in the axon reflex in the rat. 620 29


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