Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects.

Joos, Guy; Pauwels, Romain; Straeten, M. Van Der

doi:10.1136/thx.42.10.779

Cited by 215 publications

(97 citation statements)

References 24 publications

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“…Involvement of sensory neuropeptides in reflex cough has also been demonstrated by KOHROGI et al [13], TAKAHAMA et al [14] and UJIIE et al [6], who showed that substance P [13], NKA [14], and phosphoramidon [6] induced cough in the guineapig. However, a direct tussigenic effect of substance P or NKA has not yet been demonstrated in man [15]. Finally and interestingly, to demonstrate that tachykinins play a role in cough, HATHAWAY et al [16] have reported that, in heart-lung transplant patients, inhaled capsaicin was unassociated with coughing, whereas all normal and asthmatic subjects they tested coughed with capsaicin.…”

Section: Discussionmentioning

confidence: 99%

Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig

Girard¹,

Naline²,

Vilain³

et al. 1995

Eur Respir J

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E Ef ff fe ec ct t o of f t th he e t tw wo o t ta ac ch hy yk ki in ni in n a an nt ta ag go on ni is st ts s, , S SRIn conclusion, our results demonstrate that NK 2 -receptor stimulation plays a predominant role in the regulation of cough reflex, at least in the guinea-pig, as shown by the high potency and efficacy of SR 48968, a tachykinin NK 2 -receptor antagonist. SR 140333, a NK 1 -receptor antagonist is unable to inhibit cough by itself, but it potentiates SR 48968 in terms of efficiency. Finally, as salbutamol did not modify the effect of SR 48968, it may be suggested that the antitussive effect of SR 48968 is not related to the inhibition of citric acid-induced bronchoconstriction.

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Section: Discussionmentioning

confidence: 99%

Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig

Girard¹,

Naline²,

Vilain³

et al. 1995

Eur Respir J

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“…SP aerosol has given no bronchoconstrictor response in some earlier studies in guinea-pig (Dusser et al, 1988) and in man (Joos et al, 1987). However, if the SP aerosol is given in sufficiently high concentrations (about 1 mM), it induces airway narrowing in the absence of NEP inhibition (Lotvall et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Effects of aerosolised substance P on lung resistance in guinea‐pigs: a comparison between inhibition of neutral endopeptidase and angiotensin‐converting enzyme

Lötvall

Skoogh

Barnes

et al. 1990

British J Pharmacology

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1We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6mM, 60 breaths; 210nmol) to inhibit ACE and acetorphan (0.3, 1 and 3mM, 60 breaths; 9nmol, 33nmol and 110nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh).2 Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline, was calculated for each challenge. 3 Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (± 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4 Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 + 0.2 log units). 5 We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer.

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“…Whether or not the same situation applies exactly to human airways is not known, although it is suggested by some results. Thus, NK 2 receptor stimulation only mediate contraction of human isolated airways [19], and NKA but not SP produces bronchoconstriction in asthmatics [32]. Moreover, in allergic rhinitis, tachykinins induce nasal obstruction through NK 1 receptor activation, whereas albumin leakage and recruitment of inflammatory cells probably involve NK 1 and NK 2 receptors [33].…”

Section: Discussionmentioning

confidence: 99%

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

Boichot¹,

Biyah²,

Germain³

et al. 1996

European Respiratory Journal

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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],...

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Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects.

Cited by 215 publications

References 24 publications

Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig

Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig

Effects of aerosolised substance P on lung resistance in guinea‐pigs: a comparison between inhibition of neutral endopeptidase and angiotensin‐converting enzyme

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

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