Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin

Wilsoncroft, P.; Euzger, H. S.; Brain, Susan D.

doi:10.1016/0143-4179(94)90026-4

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…Tachykinins are co-stored with CGRP in sensory nerves and thus can be co-released (Lundberg et al, 1985). Oedema induced by endogenously released or exogenously injected substance P can be inhibited by NKI antagonists in the rat (Garret et al, 1991;Murai et al, 1993;Moussaoui et al, 1993) and guinea-pig (Wilsoncroft et al, 1994). Capsaicin-induced oedema in this study was not affect-ed by co-treatment with either an NK1 or NK2 antagonist.…”

Section: Discussionmentioning

confidence: 57%

“…However, the NKI antagonist, RP67850, was used at a dose of 10 nmol/site, a dose previously shown to inhibit significantly oedema induced by substance P (30 pmol/site) in the presence of a P. Newbold & S.D. Brain Capsaicin-induced oedema in rabbit skin vasodilator in guinea-pig skin (Wilsoncroft et al, 1994) and rat skin (unpublished data). The NK2 receptor antagonist, SR48968, was used at a dose of 10 nmol/site since doses of 6.5 nmol and 65 nmol injected intrathecally have been shown to inhibit neurokinin-induced nociception in the rat (Picard et al, 1993).…”

Section: Effect Of Inhibitors Of Mediators Of Increased Microvascularmentioning

confidence: 99%

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An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

Newbold

Brain

1995

British J Pharmacology

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1 Oedema formation induced by intradermal capsaicin has been studied in rabbit skin. The effect of the anti-inflammatory steroid dexamethasone and also of a range of known inhibitors of oedema formation have been investigated in order to elucidate mechanisms involved in capsaicin-induced oedema formation. 2 Oedema formation, in response to intradermally-injected test agents, was measured by the local extravascular accumulation of intravenously injected '25I-labelled albumin. In separate experiments skin blood flow was assessed by the clearance of intradermally-injected 33xenon. 3 Oedema formation induced by intradermal histamine (3 nmol) and bradykinin (1 nmol), when in the presence of vasodilator doses of calcitonin gene-related peptide (CGRP) (3 pmol) or prostaglandin El, (PGEI) (lOpmol), was significantly inhibited (P<0.01) in rabbits pretreated with intravenous dexamethasone (3 mg kg-', -4 h). In contrast dexamethasone had no effect on capsaicin (3 tmol)-induced oedema formation or, on capsaicin (30-100nmol)-induced blood flow.4 Oedema formation observed in response to intradermal capsaicin (3 ftmol) was significantly inhibited (P<0.01) when the selective capsaicin antagonist, ruthenium red (3 nmol) was co-injected. This suggests that the mechanism of capsaicin-induced oedema involves activation of sensory nerves. However, oedema was not inhibited when capsaicin was co-injected with the neurokinin NKI receptor antagonist, RP67580 (10 nmol), the NK2 antagonist SR48960 (10 nmol) or the CGRP antagonist CGRP8-37 (300 pmol).5 Oedema formation induced by capsaicin was not inhibited when co-injected with the histamine HI receptor antagonist, mepyramine (3 nmol), the PAF antagonist, WEB 2086 (100 nmol), the bradykinin B2 receptor antagonist, Hoel4O (1 nmol), or the cyclo-oxygenase inhibitor, indomethacin (10 nmol), suggesting that these mediators do not play a major role in the capsaicin-induced response. 6 Histological analysis of capsaicin-treated skin sites revealed undamaged, intact microvessels and lack of haemorrhage. Further, co-injection of capsaicin with the hydrogen peroxide remover, catalase (2,200 u), had no effect on oedema formation. This suggests that capsaicin does not induce oedema formation secondary to free radical-induced damage. 7 These results indicate that capsaicin-induced oedema in rabbit skin involves activation of sensory nerves. However, the oedema is not inhibited by pretreatment with the anti-inflammatory steroid, dexamethasone. Further the mechanisms which lead to the oedema formation observed after intradermal capsaicin remain unknown.

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Section: Discussionmentioning

confidence: 57%

Section: Effect Of Inhibitors Of Mediators Of Increased Microvascularmentioning

confidence: 99%

An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

Newbold

Brain

1995

British J Pharmacology

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“…The effects of SP on cutaneous vascular permeability have previously been described in the guinea-pig and a role for NK, receptors identified (Iwamoto & Nadel, 1989;Wilsoncroft et al, 1994). The aim of the present study was to extend these findings by addressing the role of NK, receptors in SP-induced neutrophil and eosinophil accumulation in guinea-pig skin.…”

Section: Introductionmentioning

confidence: 75%

“…The NK, receptor antagonist, CP-96,345 (Snider et al, 1991) has been shown to inhibit SPinduced plasma extravasation in guinea-pig dorsal skin and neurogenic inflammation in rats (Lembeck et al, 1992). Similarly, the NK, receptor antagonist, 580 (Garret et al, 1991) inhibits oedema formation induced by SP and in response to a passive cutaneous anaphylaxis reaction in guinea-pig skin (Wilsoncroft et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…In man, SP causes a classic wheal and flare response (Hagermark et al, 1978; as well as eliciting granulocyte infiltration (Smith et al, 1993) and modulating the activity of another neuropeptide calcitonin gene-related peptide (CGRP) (Brain & Williams, 1988). In addition, SP-induced oedema formation and leukocyte accumulation has been studied in a number of experimental animals (Matsuda et al, 1989;Yano et al, 1989;Lembeck et al, 1992;Wilsoncroft et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Substance P‐induced inflammatory responses in guinea‐pig skin: The effect of specific NK₁ receptor antagonists and the role of endogenous mediators

Walsh

Weg

Williams

et al. 1995

British J Pharmacology

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1 The sensory neuropeptide substance P (SP), when released from sensory nerves, has been implicated in the development of neurogenic inflammation. In the present study, using an in vivo model system, we have characterized and investigated the mechanisms underlying SP‐induced leukocyte accumulation and oedema formation in the guinea‐pig.2 Intradermaly injected SP (i.d., 10−13‐10−9mol per site), induced a dose‐ and time‐dependent accumulation of 111In‐neutrophils, 111In‐eosinophils and oedema formation as measured by the local accumulation of i.v. injected l25I‐albumin. The leukocyte accumulation evoked by SP was significant at 10−10 and 10−9mol per site, whereas oedema formation was significant at the lowest dose tested (10−13mol per site).3 The NK1 receptor antagonists, CP‐96,345 (1 mgkg−1, i.v.) and RP‐67,580 (10 μg per site, i.d.), significantly attenuated the oedema formation induced by the lower doses of SP. Oedema formation and leukocyte accumulation induced by 10−9mol per site SP were unaffected by either antagonist.4 SP‐elicited responses were not significantly affected by the platelet activating factor (PAF) receptor antagonist, UK‐74,505 (2.5 mgkg−1, i.v.) or the H1 histamine receptor antagonist, chlorpheniramine (10−8mol per site, i.d.). However, the 111In‐eosinophil accumulation, but not the 111In‐neutrophil accumulation or oedema formation, induced by SP was significantly inhibited by the specific 5lipoxygenase (5‐LO) inhibitor, ZM‐230,487 (10−8 mol per site, i.d.).5 The accumulation of both 111In‐neutrophils and 111In‐eosinophils induced by SP was abolished in guinea‐pigs treated i.v. with an anti‐CD 18 monoclonal antibody 6.5E F(ab′)2 (2.5 mgkg−1). The oedema response was unaffected in these animals.6 These results suggest that SP‐induced inflammatory events may be mediated via two mechanisms involving NK1 receptor‐dependent and independent pathways. Oedema formation induced by the lower doses of SP may be mediated via the direct activation of NK1 receptors whilst, at higher doses, oedema formation and leukocyte accumulation may be mediated via the release of secondary mediators, possibly mast cell derived, with 5‐LO products playing an important role in the leukocyte infiltration. The leukocyte accumulation, but not the oedema induced by SP, is dependent on the expression of the CD 18 antigen on leukocytes.

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Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin

Cited by 12 publications

References 17 publications

An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

Substance P‐induced inflammatory responses in guinea‐pig skin: The effect of specific NK₁ receptor antagonists and the role of endogenous mediators

What are the treatment options for patients with interstitial cystitis?

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Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin

Cited by 12 publications

References 17 publications

An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

An investigation into the mechanism of capsaicin‐induced oedema in rabbit skin

Substance P‐induced inflammatory responses in guinea‐pig skin: The effect of specific NK1 receptor antagonists and the role of endogenous mediators

What are the treatment options for patients with interstitial cystitis?

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Substance P‐induced inflammatory responses in guinea‐pig skin: The effect of specific NK₁ receptor antagonists and the role of endogenous mediators