Pharmacological profile of a high affinity dipeptide NK<sub>1</sub> receptor antagonist, FK888

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

doi:10.1111/j.1476-5381.1992.tb14524.x

Cited by 138 publications

(51 citation statements)

References 18 publications

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“…In the present LTD 4 studies, L-NAME partially suppressed the induced plasma leakage in central airways, and this inhibitory effect disappeared in the presence of the NK 1 receptor selective antagonist FK888 [17]. We have previously clarified the contribution of tachykinins to LTD 4 -induced plasma leakage in guinea-pig airways, in which FK888 and capsaicin pretreatment, which causes sensory neuropeptide depletion, partially inhibited the induced plasma leakage in central but not in peripheral airways [18].…”

Section: Discussionmentioning

confidence: 97%

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Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Kageyama¹,

Miura²,

Ichinose³

et al. 1997

Eur Respir J

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Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators. N. Kageyama, M. Miura, M. Ichinose, M. Tomaki, J. Ishikawa, Y. Ohuchi, N. Endoh, K. Shirato. ERS Journals Ltd 1997. ABSTRACT: This study examines the role of endogenous nitric oxide (NO) in airway microvascular leakage induced by inflammatory mediators, which play an important role in asthmatic airways.Guinea-pigs were anaesthetized and mechanically-ventilated with monitoring of arterial blood pressure, and airway microvascular leakage induced by intravenous injection of substance P (SP), leukotriene D 4 (LTD 4 ) and histamine was evaluated using Evans blue dye and Monastral blue dye in the presence and absence of the NO synthase inhibitors, L-N G -nitroarginine methyl ester (L-NAME) and L-N Gmonomethyl arginine (L-NMMA). The effect of a soluble guanylate cyclase inhibitor, LY83583, on SP-induced dye leakage was also examined.Intravenous injection of SP (1 µg·kg -1 ), LTD 4 (1 µg·kg -1 ) and histamine (100 µg·kg -1 ) significantly increased dye extravasation at all airway levels. Pretreatment with L-NAME (10 mg·kg -1 i.v.) and L-NMMA (100 mg·kg -1 i.v.) significantly inhibited SP-induced extravasation, and L-arginine (100 mg·kg -1 i.v.) reversed L-NAMEinduced inhibition. L-NAME (10 mg·kg -1 i.v.) also significantly inhibited LTD 4 -induced dye extravasation only in central airways, and this inhibitory effect was abolished by a neurokinin-1 (NK 1 ) antagonist, FK888 (10 mg·kg -1 i.v.) pretreatment. Histamineinduced dye extravasation was not affected by L-NAME. LY83583 (2.5 and 7.5 mg·kg -1 i.v.) partially but significantly reduced SP-induced dye leakage.These results suggest that endogenous nitric oxide plays a role in neurokinin-1 receptor-mediated airway microvascular leakage, and presumably involves the guanylate cyclase pathway. Eur Respir J., 1997; 10: 13-19

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Section: Discussionmentioning

confidence: 97%

“…In the second set of experiments, the effect of L-NAME on LTD 4 -induced airway microvascular leakage was again examined in the presence of NK 1 receptor antagonist, FK888 [17], since a part of LTD 4 -induced airway plasma leakage is caused by NK 1 receptor activation [18]. FK888 (10 mg·kg -1 i.v.)…”

Section: Protocolmentioning

confidence: 99%

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Kageyama¹,

Miura²,

Ichinose³

et al. 1997

Eur Respir J

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“…PIEDIMONTE et al [24] showed that CP-99,994, an antagonist of NK 1 receptors, inhibited plasma extravasation in the rat trachea produced by substance P and by stimulation of sensory nerves with capsaicin. In the present study, pretreatment of rats with capsaicin injection to deplete endogenous tachykinins or intravenous administration of the selective NK 1 receptor antagonist FK888 [16] abolished adenosine-induced plasma extravasation. These findings suggest that adenosine may stimulate the release of tachykinins from sensory nerves, which consequently activate NK 1 receptors on the endothelial cells of the postcapillary venules.…”

Section: Discussionmentioning

confidence: 98%

“…kg -1 ) was studied. The effect of FK888, a selective neurokinin-1 (NK 1 ) receptor antagonist [16], on the adenosine action was also examined. In order to do this, FK888 (10 mg .…”

Section: Methodsmentioning

confidence: 99%

Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats

Tamaoki¹,

Yamawaki²,

Taira³

et al. 1999

Eur Respir J

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Inhalation of adenosine causes bronchoconstriction in asthmatic subjects, but the effect of this purine nucleotide on airway vascular permeability is unknown.In order to determine whether adenosine produces airway microvascular leakage and, if so, to examine the effect of cromolyn (sodium cromoglycate (SCG)) on this extravasation of Evans blue was measured in the airways of ovalbumin-sensitized Brown Norway rats.Inhaled adenosine caused microvascular leakage in sensitized but not in nonsensitized rats, and the response was abolished by capsaicin pretreatment or the tachykinin neurokinin-1 receptor antagonist FK888. Adenosine-induced vascular leakage became apparent in nonsensitized rats when treated with phosphoramidon, and airway neutral endopeptidase activity was lower in sensitized than in nonsensitized animals. The extravasation induced by adenosine in sensitized rats was dose dependently inhibited by SCG aerosols. SCG likewise inhibited microvascular responses to substance P, but had no effect on those to platelet-activating factor.These results suggest that: 1) adenosine induces airway microvascular leakage in sensitized rats through stimulation of neurokinin-1 receptors; 2) this effect is associated with a sensitization-induced decrease in neutral endopeptidase activity; and 3) sodium cromoglycate inhibits adenosine-induced extravasation, presumably via functional antagonism of tachykinins. Eur Respir J 1999; 14: 1082±1087. Adenosine is a naturally occurring purine nucleotide formed by the cleavage of adenosine 5'-monophosphate by 5'-nucleotidase or by the catabolism of S-adenosylhomocysteine. Based on the findings that adenosine can be released from mast cells in both early-and late-phase asthmatic responses via antigen/immunoglobulin E (IgE) interaction after allergen bronchoprovocation [1] and that inhaled adenosine causes bronchoconstriction in asthmatics but not in normal subjects [2], this purine nucleotide is thought to play a role in the pathophysiology of asthma. Increased microvascular permeability and plasma protein extravasation in the airways might contribute to mucosal oedema, inflammatory cell infiltration and epithelial cell desquamation, which are characteristic features of asthma [3]. Previous studies have shown that adenosine induces plasma extravasation in rat skin [4] and hamster cheek pouch [5], but its effect on airway microvascular permeability is unknown.Cromolyn (sodium cromoglycate (SCG)) is an antiallergic drug and has been widely used in the treatment of asthma [6,7]. Although SCG has long been recognized as a mast cell-stabilizing agent [8], its mechanism of action in asthma is still unclear. CROSSMAN et al. [9] showed that oedema formation in the human skin produced by substance P was reduced by SCG, suggesting that SCG may modify tachykinin actions. Therefore, the purposes of the present study were: 1) to determine whether adenosine produces airway vascular leakage; 2) to elucidate the possible involvement of tachykinins in the effect of adenosine; and 3) to deter...

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“…(Fujii et al, 1992) (10-1o-10 M), (Snider et al, 1991) (101o°-10-8M), (Desai et al, 1992) Concentration (-IOgM) Figure 5 Effects of tachykinin NK1 and NK2 receptor antagonists on the endothelium-independent contraction induced by substance P (10-7M) in the endothelium-free intrapulmonary artery of the rabbit. dramine (10' M) and [Sar',Ala8]-angiotensin II (10' M) had no effect on the EIC (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂

Shirahase

Kanda

Kurahashi

et al. 1995

British J Pharmacology

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1 We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery.2 Removal of the endothelium almost abolished the contraction induced by SP (10' M) while it did not attenuate the contraction induced by SP (lI-V M), NKA (0 -l10-7 M) or NKB (10' and 10 M). 3 The EDC induced by SP (10' M) was abolished by NKI antagonists (FK-888, and SR-140333) but not by an NK2 antagonist (SR-48968). 4 The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5 The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB> SP. The EIC induced by SP (1O' M) was attenuated by an NK2 antagonist but not by NK, antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6 In conclusion, SP at 101 M induces EDC via endothelial NK, receptors and TXA2 production, and SP at 10-7 M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.

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Pharmacological profile of a high affinity dipeptide NK₁ receptor antagonist, FK888

Cited by 138 publications

References 18 publications

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂

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Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888

Cited by 138 publications

References 18 publications

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2

Contact Info

Product

Resources

About

Pharmacological profile of a high affinity dipeptide NK₁ receptor antagonist, FK888

Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK₁ receptors and TXA₂