Immunoreactive tachykinins, calcitonin gene-related peptide and neuropeptide Y in human synovial fluid from inflamed knee joints

Larsson, Johan; Ekblom, A.; Henriksson, K.; Lundeberg, Thomas; Theodorsson, Elvar

doi:10.1016/0304-3940(89)90707-6

Cited by 53 publications

(17 citation statements)

References 17 publications

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“…Recently, substance P, a decapeptide present in the nerve endings of sensory C fibres, has attracted attention as a key molecule in the regulation of inflammatory reactions including those found in RA [6][7][8][9][10]. The rationale for this proposal is that (1) substance P stimulates the release of histamine and prostaglandin E 2 from macrophage and synovial cells [9] and (2) a high concentration of this neuropeptide has been found in the joint fluid of RA patients [10].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

et al. 1996

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We examined the intracellular mechanisms of substance P induced oxyradical production in rheumatoid synovial cells by the luminol-dependent chemiluminescence method. After stimulation with substance P (30 microM), single synovial A (macrophage-like) or B (fibroblast-like) cells released oxyradicals such as superoxide anions (O2-) and/or hypochlorous anions (OCl-) under a microscope equipped with an ultrasensitive photonic image intensifier. The substance P induced oxyradical production was blocked by a tachykinin NK1 (NK1) receptor antagonist, GR82334, GTP-binding protein (G-protein) inactivators, GDP beta S and islet-activating protein (IAP), and a phospholipase C (PLC) inhibitor, U-73122. Substance P (30 microM) also induced a transient increase in the intracellular Ca2+ concentration ([Ca2+]i) in both synovial A and B cells as measured by a Ca2+ indicator, fura 2, BAPTA-AM and an inositol-1,4-5-triphosphate (IP3) receptor antagonist, heparin, inhibited the substance P induced increase in [Ca2+]i, but they had no effects on oxyradical production. In contrast to the effects of BAPTA-AM and heparin, protein kinase C (PKC) inhibitors, H-7 and calphostin C, completely inhibited substance P induced oxyradical production without any significant effects on [Ca2+]i increase. These findings suggest that the NK1 receptor/PLC-linked diacylglycerol (DAG) formation with the resulting activation of PKC is the main signal transduction pathway for substance P stimulated oxyradical production in synovial cells.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

et al. 1996

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“…Further, neuropeptides have been found in the synovial fluid of patients with rheumatoid arthritis (Larsson et al, 1989;Marshall et al, 1990) and suggested to play a role in skin diseases including psoriasis (Farber et al, 1986), blister, burn (Wallengren et al, 1986), dermatographism and cold urticaria (Wallengren et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Profile of capsaicin‐induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid‐induced ear oedema

Inoue

Nagata

Kinoshita

1993

British J Pharmacology

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1 We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2 Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3 Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 jg per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine HI and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca2+-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema.4 Phosphoramidon (50 jig kg-', i.v.), an endopeptidase inhibitor, markedly (P<0.001) enhanced only capsaicin-induced ear oedeima, but bestatin (0.5mgkg-', i.v.), an aminopeptidase, failed to enhance oedema formation. 5 Neuropeptides (1-100 pmol per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicinsensitive neurones, caused ear oedema by intradermal injection. Furthermore, a synergistic effect of CGRP (10fmol per site) and SP (1Opmol per site) on oedema formation was observed.6 The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-', p.o.), a histamine H, and 5-HT antagonist, was administered before injection. In contrast, nifedipine (50 mg kg-', p.o.), a Ca2'-channel blocker, and indomethacin (10 mg kg-', p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on neuropeptideinduced oedema. 7 These results suggest that the mechanism of capsaicin-induced ear oedema is different from that of AA-induced oedema and suggest that the development of capsaicin-induced ear oedema is primarily mediated by neuropeptides. The neuropeptides released after activation of sensory nerves cause an increase of vascular permeability by interactions with endothelial cells and by histamine release from mast cells.

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“…Substance P could not be demonstrated in RA patients and controls with early meniscus degenerations or ligamentous lesions [97,98]. NKA, CGRP, and NPY results were also variable.…”

Section: Rheumatoid Arthritis and Osteoarthritismentioning

confidence: 54%

Substance P in Rheumatic Diseases

Seidel

Tsalik²,

Vetter³

et al. 2007

CRR

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Inflammation in many autoimmune syndromes is modulated by the nervous system. This paper reviews important principles of neurogenic inflammation and findings of substance P overexpression in rheumatic diseases. Substance P is a key molecule in activating inflammation after antidromal axoplasmic transport and secretion at the nociceptor. We summarize the results from studies with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, systemic lupus erythematodes, systemic sclerosis, vasculitides, Sjögren syndrome, vasculitides, reflex sympathetic dystrophy, gouty arthritis, fibromyalgia syndrome, chronic fatigue syndrome and degenerative vertebral spine disorders. Although substance P is associated with many of these diseases, selective receptor blockers have not been effective in therapy. In contrast, the nonselective antagonist capsaicin is beneficial in some conditions. We also discuss a novel therapeutic principle with selective serotonin antagonists that may induce a powerful downregulation of neurogenic inflammation.

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Immunoreactive tachykinins, calcitonin gene-related peptide and neuropeptide Y in human synovial fluid from inflamed knee joints

Cited by 53 publications

References 17 publications

Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

Profile of capsaicin‐induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid‐induced ear oedema

Substance P in Rheumatic Diseases

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