NK2 receptors mediate plasma extravasation in guinea‐pig lower airways

Tousignant, Christine; Chen, Chan; Guévremont, Diane; Brideau, Christine; Hale, Jeffrey J.; MacCoss, Malcolm; Rodger, Ian W.

doi:10.1111/j.1476-5381.1993.tb12813.x

Cited by 61 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This effect appears markedly significant in the trachea, main bronchi and in proximal intrapulmonary airways, but not significant in the distal intrapulmonary airway, suggesting that the NK 1 receptor might be less involved in the lower airways than in the tracheobronchial region. These results might support the observations of TOUSIGNANT et al [14], that NK 2 rather than NK 1 may be involved in lower airways. However, we did not observe a reduction of the potentiation of histamine-induced microvascular leakage by SP in distal pulmonary airways, under the treatment of SR 48968…”

Section: Discussionsupporting

confidence: 83%

“…Moreover, NK 1 receptor stimulation has been reported to be involved in the delayed-type hypersensitivity induced increase in vascular permeability in the mouse small intestine [28], and in the SP-induced inflammatory responses in guinea-pig skin [29]. Otherwise, NK 2 receptor stimulation may also be involved in airway plasma protein extravasation, namely in distal airways [14].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have indicated that tachykinin NK 1 -receptors are involved in the neurogenic inflammation in the central airways of guinea-pigs and rats [12,13]. Nevertheless, a role for NK 2 receptors in microvascular leakage cannot be totally excluded, since it was recently demonstrated that NKA may induce plasma protein extravasation in guinea-pig secondary bronchi and intraparenchymal airways, via NK 2 receptor stimulation [14].…”

Section: Involvement Of Tachykinin Nkmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of tachykinin NK1 and NK2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs

Boichot¹,

Biyah²,

Germain³

et al. 1996

European Respiratory Journal

View full text Add to dashboard Cite

Involvement of tachykinin NK 1 and NK 2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs. E. Boichot, K. Biyah, N. Germain, X. Emonds-Alt, V. Lagente, C. Advenier. ©ERS Journals 1996. ABSTRACT: Tachykinins, such as substance P, might be involved in the development of airway hyperresponsiveness (AHR) and airway inflammation. However, it is unknown which tachykinin receptors mediate these biological activities. The effects of two antagonists of tachykinin neurokinin-1 (NK 1 ) and tachykinin neurokinin-2 (NK 2 ) receptors, SR 140333 and SR 48968, respectively, were investigated on substance P (SP)-induced airway hyperresponsiveness and potentiation of the histamine-induced increase in microvascular leakage, in phosphoramidon-pretreated guinea-pigs.Guinea-pigs were pretreated with phosphoramidon (0.1 mM aerosol for 15 min) and exposed 15 min later to saline solution alone or to saline solution containing SP (0.1 mg·mL -1 for 30 min). Twenty four hours later, the animals were anaesthetized and prepared for the recording of the pulmonary inflation pressure (PIP) to acetylcholine or for the investigation of microvascular leakage to histamine.Pretreatment of the guinea-pigs with a single dose of SR 48968 (1 mg·kg -1 , i.p.) 30 min before SP exposure, significantly prevented the development of AHR, whereas SR 140333 (1 mg·kg -1 , i.p.) did not. In a second set of experiments, phosphoramidon-pretreated guinea-pigs exposed to SP presented a significant potentiation of the histamine-induced increase in microvascular leakage in pulmonary airways. When the guinea-pigs were pretreated with SR 140333, an inhibition of the increased microvascular leakage to histamine was observed. In contrast, no significant inhibitory activity was noted when the guinea-pigs were pretreated with SR 48968.The present data demonstrate the importance of tachykinin NK 2 receptor stimulation in the development of airway hyperresponsiveness and that of tachykinin NK 1 receptor stimulation in microvascular leakage hypersensitivity in phosphoramidonpretreated and substance P-exposed guinea-pigs. The results also suggest a dissociation between the presence of microvascular leakage and the occurrence of airway hyperresponsiveness. Eur Respir J., 1996Respir J., , 9, 1445Respir J., -1450 Among the different inflammatory mediators suspected of playing a role in airway hyperresponsiveness (AHR) and airway inflammation, several lines of evidence suggest that tachykinins, such as substance P (SP) and neurokinin A, might be involved. Indeed, recent studies have reported that exposure of guinea-pigs to an aerosol of capsaicin or substance P, substances that release endogenous sensory neuropeptides, such as SP, elicited AHR to exogenous bronchoconstrictor agents [1][2][3][4]. Conversely, a chronic treatment with high doses of capsaicin, which depletes tachykinins from nonadrenergic noncholinergic nerves, eliminates AHR to methacholine or histamine induced by acute capsaicin [2], ovalbumin [5],...

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Involvement Of Tachykinin Nkmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of tachykinin NK1 and NK2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs

Boichot¹,

Biyah²,

Germain³

et al. 1996

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…Many studies have demonstrated that tachykinin-induced contraction of airway smooth muscle is mainly due to the activation of NK 2 receptors [1,18]. Furthermore, both NK 1 and NK 2 receptors may participate in producing the exudative responses to tachykinins in guinea pig airways [31,38]. Hence, our observations are in agreement with the current viewpoint regarding the roles of NK 1 and NK 2 receptors in producing neurogenic airway responses.…”

Section: Discussionsupporting

confidence: 82%

Involvement of Tachykinin NK1 and NK2 Receptors in Changes in Lung Mechanics and Airway Microvascular Leakage during the Early Phase of Endotoxemia in Guinea Pigs

Tang¹,

Yang²,

Kou³

2002

J Biomed Sci

View full text Add to dashboard Cite

We investigated the role of tachykinins in airway neurogenic responses occurring in the early phase of endotoxemia. Forty-eight anesthetized guinea pigs were evenly divided into six groups pretreated with either saline vehicle, CP-96,345 (a tachykinin NK₁ receptor antagonist), SR-48,968 (a tachykinin NK₂ receptor antagonist) or CP-96,345 and SR-48,968 in combination. Animals then received an intravenous injection of either saline (the vehicle for endotoxin) or endotoxin (30 mg/kg). Total lung resistance (R_L) and dynamic lung compliance (C_dyn) were continuously measured before and 30 min after administration of saline or endotoxin. Airway microvascular leakage was assessed at the end of the observation period. Endotoxin significantly increased R_L and decreased C_dyn 10 min after intravenous endotoxin injection. Plasma extravasation significantly increased in the trachea, main bronchi and intrapulmonary airways with endotoxin administration. These changes in lung mechanics were abolished by SR-48,968, but were unaffected by CP-96,345. The plasma extravasation was largely attenuated by CP-96,345 and/or SR-48,968. We conclude that (1) endogenous tachykinins play an important role in producing changes in lung mechanics and airway microvascular leakage during the early phase of endotoxemia and (2) activation of tachykinin NK₂ receptors is responsible for the former response, while activation of both tachykinin NK₁ and NK₂ receptors is involved in the latter response.

show abstract

“…TOUSIGNANT et al [92] recently reported that [β-Ala 8 ]NKA(4-10) may induce plasma protein extravasation in guinea-pig secondary bronchi and intraparenchymal airways, via tachykinin NK 2 receptor stimulation.…”

Section: Tachykinins and Microvascular Leakagementioning

confidence: 99%

The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough

Advenier¹,

Lagente²,

Boichot³

1997

Eur Respir J

113

View full text Add to dashboard Cite

The excitatory nonadrenergic noncholinergic (NANC) system, involving various neuropeptides of the tachykinin family, such as substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP), as transmitters, has now been well characterized. In airways, SP, NKA and CGRP are co-localized in the sensory unmyelinated C-fibres, which innervate all compartments of the airway wall from the trachea down to the bronchioles. C-fibre endings are found within the epithelium. They form a dense plexus in the subepithelial lamina propria, supply the glands, ramify within the smooth muscle layer and make direct contacts with postganglionic parasympathetic neurons, located in the local ganglion. In the trachea, this sensory innervation is almost exclusively derived from sensory vagal neurons, supplied by the jugular ganglion, whilst that of the lung is of mixed origin with a predominating vagal and a smaller spinal contribution [1][2][3][4][5]. The NANC system can be activated by different stimuli, which affect the chemosensitive C-fibre afferents in airways and lead to a local release of tachykinins that are responsible for several biological effects in the bronchopulmonary system: bronchospasm; increase in vascular permeability from postcapillary venules; stimulation of glandular secretion; facilitation of cholinergic neurotransmission; and recruitment and activation of some types of inflammatory cells. Sensory nerves also mediate respiratory defence reflexes, such as coughing, sneezing and secretion of mucus ( fig. 1).From these data, it has been hypothesized that abnormal stimulation of the sensory nerve terminals, e.g. induced by epithelial shedding as seen in asthma, results in enhanced release of tachykinins in the airway wall with subsequent exaggeration of inflammation. This concept of "neurogenic inflammation" introduces sensory nerve fibres as important components in the pathogenesis of asthma.The biological actions of tachykinins are mediated via three types of receptors, denoted neurokinins 1-3 (NK 1 , NK 2 and NK 3 ), which have the highest affinity for SP, NKA and NKB, respectively. This receptor classification has been established from receptor-binding and functional studies. It has now been recognized that the expression of tachykinin NK 3 receptors is confined mainly to the central and peripheral nervous system, whilst tachykinin NK 1 and tachykinin NK 2 receptors are expressed both in the central and peripheral nervous system and in target organs, including airways [5][6][7][8][9][10]. According Taken together, the results obtained with the various selective receptor antagonists provide pharmacological evidence that tachykinins play a role in delayed bronchopulmonary alterations and suggest that tachykinin receptor antagonists may be useful for investigating mechanisms and possibly reducing airway functional alterations in asthmatic patients. PHARMACOLOGICAL REVIEW

show abstract

NK₂ receptors mediate plasma extravasation in guinea‐pig lower airways

Cited by 61 publications

References 24 publications

Involvement of tachykinin NK<SUB>1</SUB> and NK<SUB>2</SUB> receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs

Involvement of tachykinin NK<SUB>1</SUB> and NK<SUB>2</SUB> receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs

Involvement of Tachykinin NK<sub>1</sub> and NK<sub>2</sub> Receptors in Changes in Lung Mechanics and Airway Microvascular Leakage during the Early Phase of Endotoxemia in Guinea Pigs

The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough

Contact Info

Product

Resources

About