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 contribution of the neuropeptide substance P to the pathogenesis of rheumatoid arthritis (RA) has recently been suggested. The presence of immunoreactive substance P in the serum and joint fluid of RA patients was significantly increased compared with age-matched control patients. To investigate the ability of substance P to alter lymphocyte activity during the disease, lymphocytes were isolated from the synovial fluid and blood of RA patients and their ability to respond to substance P as measured by [3H]thymidine uptake was characterized. Upon exposure of RA synovial fluid and peripheral blood lymphocytes to various concentrations of substance P in vitro, no increase in proliferation was witnessed. To the contrary, control peripheral blood lymphocyte proliferation was significantly enhanced by various concentrations of substance P. However, synoviocytes from the joints of RA patients were responsive to substance P stimulation. These data suggest that substance P receptors may be desensitized on systemic and local lymphocytes in RA, or the proinflammatory activities of substance P may be mediated via the synovial membrane during chronic inflammation.
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PMID:Are lymphocytes a target for substance P modulation in arthritis? 137 12

Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu-enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta-end and that opioid peptides are related to the degree of inflammation in RA.
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PMID:[A study of opioid peptides in synovial fluid and synovial tissue in patients with rheumatoid arthritis]. 152 70

To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.
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PMID:Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis. 153 34

Recent studies have shown that neuropeptides, such as substance P, are responsible for arthritis. We therefore studied opioid peptides (beta-endorphin, Methionine-enkephalin, Leucine-enkephalin) in order to confirm our belief that mental status may have some influence on the activity of rheumatoid arthritis (RA). We examined opioid peptides, lymphocyte subsets, psycologic test (Cornell Medical Index-Health questionnaire (CMI), the Face scale) and clinical data in patients with RA. Plasma Leu-enk, % Leu2a+ Leu15- cells,% Leu3a+ Leu8- cells and % Leu11+ Leu7- cells were higher in patients with a larger number of psycologic complaints in CMI. Plasma Leu-enk concentration was higher while % Leu11+ Leu7- cells was lower in proportion to the degree of neurosis, as indicated by the descrimitive chart of CMI. Plasma Met-enk concentration, % Leu2a+ Leu15- cells, and Lansbury's index were significantly higher in the group of patients whose facial expression was more severe. These findings suggest that mentala status have some relationship with the plasma level of opioid peptides (enkephalins) and immunologic functions, and that it may exert indirect effects on RA.
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PMID:[Psychosomatic medicine in rheumatoid arthritis]. 158 48

Recent evidence suggests an important role for kinins in the generation of pain, swelling and the cellular damage associated with inflammatory joint disease. Kinins are considered to be pro-inflammatory peptides for a variety of reasons. They stimulate c fibres in the synovium to cause pain and increase extravasation of fluid to produce swelling. Kinins possess the capacity to release neurotransmitters (substance P, acetylcholine) and a second wave of mediators (interleukin-1, tumour necrosis factor, interleukin-8, prostaglandins, leukotrienes). The steady levels and turnover of kinins is regulated by formation (enzymic action of kininogenases on endogenous substrates called kininogens) and by metabolism (kininases, peptidases that hydrolyse kinins). These components of the kinin system can enter the synovial joint space either by transudation from the plasma or from degranulating neutrophils chemotactically attracted into the synovium from which they migrate into the synovial fluid. If kinins are involved, one would expect neutrophil derived mediators of the system to dominate in rheumatoid arthritis and psoriatic arthritis and plasma derived products to be more important in osteoarthritis and gout. But, the question whether any of the functions attributed to each component of the system can be considered to be a primary factor in the cellular pathology of inflamed joints remains to be established. Future investigations, including therapeutic trials with kinin antagonists and kallikrein inhibitors, will need to address the differential role of the kallikreins and kinins in the different types of synovitis, on symptoms of inflammation and on any remedial effects on the progression of tissue damage within the joint.
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PMID:Kinins--key mediators in inflammatory arthritis? 164 49

Topical capsaicin has been introduced in the U.S. and Canada as a cream indicated for temporary relief of neuralgia following episodes of herpes zoster infections and in the treatment of diabetic neuropathy. Although capsaicin is clinically used as an external analgesic for temporary relief of neuralgia, it has also been widely used as a research tool to study peripheral pain. Capsaicin apparently works to release substance P from sensory nerve fibers and after repeated applications, depletes neurons of substance P. Clinical investigations of topical capsaicin include trials in chronic pain syndromes such as postherpetic neuralgia, postmastectomy neuroma, reflex sympathetic dystrophy syndrome, diabetic neuropathy, rheumatoid arthritis, psoriasis, hemodialysis-associated itching, and vulvar vestibulitis. In addition, therapeutic benefits of capsaicin cream on apocrine chromhidrosis have been described. Further clinical studies are warranted in several of these conditions to establish the efficacy of topical capsaicin. Serious or unexpected adverse reactions from clinical use have not been reported to date. Considering the paucity of safe and effective treatments for the conditions mentioned above, capsaicin cream appears to warrant further clinical investigations to establish its efficacy in a variety of chronic pain syndromes.
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PMID:Topical capsaicin in dermatologic and peripheral pain disorders. 165 16

The uncadecapeptide substance P (SP), which is localized in peripheral and central terminals of afferent nerve fibers with polymodal nociceptors, has recently been implicated as having a neurogenic, inflammatory role in experimental arthritis. We used a radioimmunoassay to measure SP levels in plasma and synovial fluid samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome (RS), and posttraumatic arthritis, as well as in plasma samples from 13 normal subjects. Plasma SP levels in RS patients exceeded levels in RA and OA patients, which in turn exceeded levels in posttrauma patients and in normal subjects. Synovial fluid SP levels exceeded respective plasma levels for all groups, except in RS patients, in whom the plasma level was not significantly different from that in synovial fluid. SP levels in synovial fluid of RA, OA, and RS patients did not differ significantly from each other, but the level in posttrauma patients was higher than in all other groups (P less than 0.005). These studies demonstrate localized intraarticular SP release, and significant plasma/synovial fluid SP concentration gradients in several forms of arthritis.
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PMID:Substance P and arthritis: analysis of plasma and synovial fluid levels. 168 61

Substance P (SP) is an 11-amino-acid neuropeptide found in sensory neurons in the peripheral nervous system. In addition to having well-characterized functions as a peptide neurotransmitter, it also plays a major role in modulating inflammatory and immune responses. SP can alter the proliferative and physiological responses of both lymphocytes and macrophages. These effects are mediated by specific high-affinity SP receptors which have been characterized both kinetically and biochemically. The principle SP binding protein present on human lymphocyte cell membranes is a 58,000-MW hydrophobic glycoprotein. Cellular responses subsequent to the binding of substance P to its receptor that have been identified in various cell populations include phosphatidyl inositol turnover, arachidonic acid metabolism, immunoglobulin synthesis, and enzyme production and secretion. Evidence also suggests that SP modulation of inflammation is a factor in the pathophysiology of certain diseases such as rheumatoid arthritis.
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PMID:Immunomodulation by tachykinin neuropeptides. 169 81

Peripheral mononuclear cells taken from rheumatoid arthritis (RA) patients, which had previously been treated in vitro with the neuropeptide Substance P (SP) followed by stimulation with the mitogen PHA, showed a significantly higher percent positivity of lymphocytes with the double-markers CD4+ CD2+, CD8+ CD25+, CD4+, HLA-DR+ and CD8+ HLA-DR+ than those of the cells untreated by SP. No effect of SP was detected in normal controls, except that the cells with the double-marker CD4+ CD25+ were slightly increased. Furthermore, in RA patients the percentage of CD4+ CD45R- cells was increased, while that of CD4+ CD45R+ cells was decreased, by pre-treatment with SP and stimulation with PHA. Monocytes of patients with rheumatoid arthritis after the treatment with SP released a significantly higher amount of oxygen-intermediate than those of normal controls with or without SP. From these results, it could be considered that SP plays an important role in RA inflammation.
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PMID:Role of lymphocyte activation by substance P in rheumatoid arthritis. 169 65

By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis. 170 Aug 40


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