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

Many atopic dermatitis (AD) patients have exacerbations of their skin disease in winter. These exacerbations may be caused by non-immunological 'non-specific' factors, such as low sun exposure and low temperature. To date, the influence of season on non-specific skin reactivity in AD has not been studied. The aim of the present investigation was to assess the influence of season on two skin parameters which may be used as quantitative measures of non-specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous irritant (sodium lauryl sulphate, SLS) exposure, and (ii) weal and flare responses to intracutaneous injection of bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin). Four of 16 AD patients had dermatitis which was more severe in November than in July. Susceptibility to SLS was increased in November, both in AD patients and in control subjects. AD patients were more susceptible to SLS than control subjects in both July and November. Pre-exposure barrier function and skin hydration were reduced in November. The increased irritant susceptibility in November may be attributed to reduced barrier function, reduced skin hydration, and/or absence of the beneficial effects of ultraviolet light on cellular targets beneath the stratum corneum. Flare responses to codeine, methacholine, substance P and trypsin were also increased in November compared with July, especially in AD patients. However, smaller flares were observed in AD patients than in control subjects, in both July and November. Flare values were negatively correlated with dermatitis severity, probably because of down-regulation. Weal responses did not show a clear seasonal variation. Hence, susceptibility to epicutaneous irritants and reactivity to intracutaneously injected bioactive agents are parameters which may be used to monitor season-dependent changes in non-specific skin reactivity.
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PMID:Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. II. Influence of season. 854 89

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

Alopecia areata (AA) is a dermatosis involving the sudden occurrence of bald patches on the scalp. Although the aetiology is unknown, experimental data indicate that cutaneous microcirculation plays an important role. The skin is richly innervated by neuropeptidergic sensory nerves that help regulate microvascular circulation. This study shows a reduction of cutaneous levels of substance P and calcitonin gene-related peptide (CGRP) but not of vasoactive intestinal polypeptide in scalp biopsies from patients with AA. Laser-Doppler flowmetry was used to study microcirculation of the scalp. Results indicate that patients with AA have lower basal blood flow and greater vasodilatation following intradermal CGRP injection than control subjects. A vascular hyper-reactivity to vasodilatatory substances such as neuropeptides, probably because of the lack of these substances, is hypothesized.
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PMID:Possible involvement of neuropeptidergic sensory nerves in alopecia areata. 917

The presence of neuropeptides and their specific receptors has been detected in the skin and the epithelial tissues. They are involved in innervation, immunomodulation, glandular secretion, control of cellular proliferation and regulation of blood flow. The fact that they act in so many different ways means that neuropeptides and their agonists and antagonists are now being regarded as potential therapeutic agents in dermatologic diseases. Among the substances which act as antagonists, particular attention should be paid to capsaicin, which has therapeutic potential for three types of indication: peripheral neurologic pain, affections with a neurogenic inflammatory component and pruriginous dermatosis; peptide T with therapeutic potential for psoriasis; and spantide, which might prove useful in dermatoses related to substance P. The influence of topical corticosteroids on the mechanism of action of neuropeptides can explain its efficacy in the treatment of many dermatoses. Among the agonists, the possibility of taking advantage of the vasodilatory activity of the calcitonin gene-related peptide is being considered in Raynaud's disease and erectile disfunction of the penis; and the immunomodulatory and anti-inflammatory action of the alpha-melanocyte stimulating hormone is being studied as a potential means of controlling inflammatory dermatoses of immunological origin.
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PMID:[Neuropeptides in dermatologic therapy]. 927 77

Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.
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PMID:Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation. 953 83

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.
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PMID:Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis. 1114 11

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.
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PMID:Pathogenesis of acne. 1147 71

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. To examine the possible involvement of neurogenic factors in the etiology of acne, we used immunohistochemistry to compare the distribution of SP-containing nerve fibers around sebaceous glands and the expression of neutral endopeptidase in sebaceous acini of the facial skin of acne patients and of healthy subjects. More numerous substance P immunoreactive nerve fibers in close apposition to the sebaceous glands and an increase in expression of neutral endopeptidase in sebaceous acini were observed in acne patients compared with the controls. Immunoelectron microscopy revealed that the subcellular localization of neutral endopeptidase was restricted to the Golgi apparatus and the endoplasmic reticulum within sebaceous germinative cells. In addition, in vitro experiments using an organ culture system demonstrated that substance P induced expression of neutral endopeptidase in sebaceous glands in a dose dependent manner. This study reveals that substance P and its degrading enzymes are involved in the pathogenesis of acne, which in turn might partially explain the pathologic significance of neurogenic and psychogenic aspects in the disease process.
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PMID:Sebaceous glands in acne patients express high levels of neutral endopeptidase. 1210 63

Cutaneous neurogenic inflammation is a complex biological response of the host immune system to noxious stimuli. Present evidence suggests that zinc metalloproteases may play an important role in the regulation of neurogenic inflammation by controlling the local availability of neuropeptides, such as substance P (SP), that are capable of initiating or amplifying cutaneous inflammation after release from sensory nerves. To address the hypothesis that the dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) is capable of modulating skin inflammation, we have analyzed murine allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) using wild-type C57BL/6J (ACE(+/+)) or genetically engineered mice with a heterozygous deletion of somatic ACE (ACE(+/-)). In 2,4-dinitro-1-fluorobenzene-sensitized ACE(+/-) mice, ACD was significantly augmented in comparison to ACE(+/+) controls as determined by the degree of ear swelling after exposure to hapten. Likewise, systemic treatment of ACE(+/+) mice with the ACE inhibitor captopril before sensitization or elicitation of ACD significantly augmented the ACD response. In contrast, local damage and neuropeptide depletion of sensory nerves following capsaicin, injection of a bradykinin B(2), or a SP receptor antagonist before sensitization significantly inhibited the augmented effector phase of ACD in mice with functionally absent ACE. However, in contrast to ACD, the response to the irritant croton oil was not significantly altered in ACE(+/-) compared with ACE(+/+) mice. Thus, ACE by degrading bradykinin and SP significantly controls cutaneous inflammatory responses to allergens but not to irritants, which may explain the frequently observed exacerbation of inflammatory skin disease in patients under medication with ACE inhibitors.
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PMID:Modulation of cutaneous inflammation by angiotensin-converting enzyme. 1264 55

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.
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PMID:The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice. 1625 75


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