Inhaled substance P induces activation of alveolar macrophages and increases airway responses in the guinea-pig

The role of sensory nerve endings in nerve growth factor‐induced airway hyperresponsiveness to histamine in guinea‐pigs

“…This is corroborated by studies in which exogenously applied substance P also resulted in an increase of airway reactivity to histamine (Boichot et al, 1993;Kraneveld et al, 1997). Interestingly, exogenous substance P not only aects airway reactivity to histamine, but also to cholinergic stimuli (Boichot et al, 1993;Daoui et al, 2000). This suggests that NGF, through the action of substance P, may be involved in non-speci®c airway hyperresponsiveness as seen in asthmatics (van~Schoor et al, 2000).…”

Prevention by the tachykinin NK2 receptor antagonist, SR 48968, of antigen‐induced airway hyperresponsiveness in sensitized guinea‐pigs

“…It has also been suggested that tachykinins are involved in the development of AHR (Hsuie et al, 1992; Boichot et al, 1993). The present finding that the antagonist SR 48968 prevented antigen-induced AHR in sensitized guinea-pigs, an effect which could not be attributed to functi4onal antagonism of acetylcholine-induced bronchoconstriction (Boichot et al, 1993) and an increased responsiveness to NK2 receptor stimulation of alveolar macrophages from sensitized guinea-pigs has been demonstrated (Brunelleschi et al, 1992). Regarding an effect on nerve transmission, Fischer et al (1994) have recently demonstrated that sensitization of guinea-pigs to ovalbumin induced a 1-5 fold increase of neuropeptide-concentration in lung tissue and also increased two fold the substance P/ neurokinin A-immunoreactive neurones in the nodose ganglion 24 h after allergen challenge.…”

“…Among the different inflammatory mediators involved, several lines of evidence suggest that tachykinins, such as substance P and neurokinin A might be involved in the pathogenesis of AHR. Indeed, recent studies have reported that exposure of guinea-pigs to an aerosol of either capsaicin, a substance releasing endogenous sensory neuropeptides, or of substance P elicited AHR to exogenous bronchoconstrictor agents (Hsuie et al, 1992;Boichot et al, 1993). Conversely, chronic treatment with high doses (i.p.)…”

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

“…Hartley guinea-pigs of either sex (350-400 g) (Charles River, St Aubin les Elboeuf, France) were separated at random into different groups and were exposed to an aerosol of phosphoramidon (to inhibit SP metabolism) and SP, as described previously [4]. Briefly, they were placed in a plexiglass chamber (30 × 50 × 30 cm) and exposed to an aerosol of phosphoramidon (0.1 mM) for 15 min.…”

“…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], toluene diisocyanate [6], endotoxin [7], or plateletactivating factor [8].…”