Effects of an NK1 receptor antagonist, FK888, on constriction and plasma extravasation induced in guinea pig airway by neurokinins and capsaicin

Murai, Motohiko; Maeda, Yasue; Hagiwara, Daijiro; Miyake, Hiroshi; Ikari, Norihiro; Matsuo, Masaaki; Fujii, Takashi

doi:10.1016/0014-2999(93)90220-c

Cited by 25 publications

(12 citation statements)

References 19 publications

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“…Airway oedema is an important component of airway obstruction, both in asthma and in chronic airflow limitation, but is not susceptible to acute reversal by conventional bronchodilator agents. Inhibition of airway oedema by NK, receptor antagonists, including FK888, has been demonstrated in animal models (Eglezos et al, 1991;Lei et al, 1992;Delay-Goyet et al, 1992;Hirayama et al, 1993;Murai et al, 1993 (Maggi et al, 1990). Endothelium-dependent vasodilation, as in the systemic circulation, is NK, receptor mediated, while endothelium-independent vasoconstriction is predominantly NK2 receptor mediated.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, in animals, airway oedema induced by exogenous or endogenously released tachykinins is mediated almost entirely by NK, receptors (Lembeck et al, 1992; ' Author for correspondence. Murai et al, 1993), and NK1 receptors have been implicated in airway oedema induced by environmental agents such as cigarette smoke and allergen challenge (Delay-Goyet et al, 1992;Bertrand et al, 1993). NK, receptor activation also increases mucous secretion in human and guinea pig airways (Rogers et al, 1989;Kuo et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

Walsh

Salmon

Featherstone

et al. 1994

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

Walsh

Salmon

Featherstone

et al. 1994

British J Pharmacology

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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: 47%

“…In other systems, capsaicin induces microvascular leakage by release of tachykinins from sensory nerves (Murai et al, 1993;Moussaoui et al, 1993). Tachykinins are co-stored with CGRP in sensory nerves and thus can be co-released (Lundberg et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

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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“…(c) Antibodies to the same NK-1R cytosolic region can vary in specificity and affinity. By revealing the precise location and distribution of NK-1R in the lung, selective NK-1R antagonists can be applied more effectively as potential inhibitors of mucus hypersecretion (MEN 11467; Khan et al 2001) and plasma extravasation (CP 99,994;Ball et al 1993), FK 888 (Murai et al 1993). Non-selective antagonists such as FK 224, which are active on both NK-1 and NK-2 receptor sites and can block both plasma extravasation and bronchoconstriction (Regoli et al 1994), may also be useful for respiratory diseases such as asthma or COPD.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Substance P Receptor (Neurokinin-1 Receptor) in Normal Ovine Lung and During the Progression of Bronchopneumonia in Sheep

Grubor

Ramírez-Romero

Gallup

et al. 2004

J Histochem Cytochem.

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S U M M A R Y Substance P contributes to the physiological homeostasis of pulmonary airways and vasculature. During pneumonia, alterations in substance P production and receptor expression can influence bronchoconstriction and vascular perfusion. The distribution of substance P receptor [neurokinin-1 receptor (NK-1R)] in lungs of normal sheep and sheep with acute (1 day), subacute (15 days), and chronic (45 days) bronchopneumonia caused by Mannheimia haemolytica was determined by immunohistochemistry (IHC). Three rabbit polyclonal antibodies generated to the same cytosolic C-terminal portion of NK-1R (residues 393-407) were tested. NK-1R immunoreactivity was traced in digital images and quantified with IPLAB software. There were no significant differences in NK-1R protein density between normal and infected lambs. Antibody 1 had the broadest distribution and intensity, and stained alveolar septae, smooth muscle cells of airways and vessels, epithelial cells of airways and alveoli, and submucosal glands. When all animals from the study were included, there was a trend towards decreased NK-1R immunoreactivity over time. The work suggests that (a) the density of NK-1R does not change during progression of bacterial ( M. haemolytica ) bronchopneumonia, (b) NK-1R is widely distributed in ovine lung and decreases with age, and (c) antibodies to the same NK-1R cytosolic region can vary in specificity and affinity.

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Effects of an NK1 receptor antagonist, FK888, on constriction and plasma extravasation induced in guinea pig airway by neurokinins and capsaicin

Cited by 25 publications

References 19 publications

Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

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

Distribution of Substance P Receptor (Neurokinin-1 Receptor) in Normal Ovine Lung and During the Progression of Bronchopneumonia in Sheep

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Effects of an NK1 receptor antagonist, FK888, on constriction and plasma extravasation induced in guinea pig airway by neurokinins and capsaicin

Cited by 25 publications

References 19 publications

Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung

Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung

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

Distribution of Substance P Receptor (Neurokinin-1 Receptor) in Normal Ovine Lung and During the Progression of Bronchopneumonia in Sheep

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Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung