Neurokinin A‐LI release after antigen challenge in guinea‐pig bronchial tubes: influence of histamine and bradykinin

Abstract

1 Our aim was to determine if antigen challenge stimulates sensory nerves and provokes the release of tachykinins. The involvement of histamine and bradykinin was studied by using speci®c receptor antagonists. Capsaicin-induced responses were also examined. Experiments were performed in vitro on tracheal and bronchial preparations from ovalbumin-sensitized guinea-pigs. 2 Characterization of ovalbumin-induced contraction, with regard to histamine and bradykinin, was carried out on airway ring preparations in the presence of phosphoramidon. The histamine H 1 receptor antagonist pyrilamine reduced allergen-induced bronchial contractions by about 30%, whereas the bradykinin B 2 receptor antagonist icatibant (Hoe 140) did not signi®cantly aect the response. Combined treatment with pyrilamine (1 mM) and icatibant (0.1 mM) reduced the contractions by about 80%, indicating a synergistic inhibitory action. Tracheal preparations were not signi®cantly aected by treatments, neither were capsaicin-induced contractions. 3 To study the out¯ow of tachykinins, we used a perfused bronchial-tube preparation, allowing simultaneous measurement of smooth muscle tension and mediator release. Neurokinin A-like immunoreactivity (NKA-LI) and substance P-like immunoreactivity (SP-LI) were determined by radioimmunoassay. 4 The results of the perfusion study showed an increased out¯ow of NKA-LI into the perfusate in response to ovalbumin (127% of basal) challenge. SP-LI determined in some of the samples showed a much lower amount (40 to 70 times lower) of SP-LI than NKA-LI. Treatment with icatibant and pyrilamine, separately and in combination, signi®cantly reduced the ovalbumin-induced NKA-LI out¯ow by 38%, 26% and 22%, respectively. 5 Capsaicin-induced out¯ow (124% of basal) was not signi®cantly aected by treatments (icatibant 121%, pyrilamine 107% and combined treatment 111% of basal). However, when pyrilamine was present the increased out¯ow was not statistically signi®cant. 6 In conclusion, we found that allergen provocation of guinea-pig bronchi caused an increased out¯ow of NKA-LI that was reduced by treatment with both pyrilamine and icatibant. These ®ndings demonstrate that the allergen-induced release of histamine and bradykinin stimulate sensory nerves and thereby increase out¯ow of tachykinins that contribute to the allergic reaction.

A new class of nitric oxide‐releasing derivatives of cetirizine; pharmacological profile in vascular and airway smooth muscle preparations

“…Both preparations are in vitro models for acute, mast cell‐driven, antigen‐induced, contractions and the mediators of these contractile responses ( Jonsson and Dahlén, 1994 ) are those established for the anaphylactic contraction of human airways in vitro and in vivo , namely histamine and leukotrienes ( Björck and Dahlén, 1993 ; Roquet et al ., 1997 ). In the trachea, the histamine component of the antigen‐induced contraction dominates ( Lindstrom and Andersson, 1997 ), whereas in the GPLP, antihistamines alone have no inhibitory effect on the antigen‐induced contraction ( Jonsson and Dahlén, 1994 ). It was hypothesized that interactions between a H1 histamine receptor antagonist and a NO‐donor thus effectively could be evaluated in the antihistamine‐sensitive GPT.…”

NK2 Receptor-Mediated Spontaneous Phasic Contractions in Normal and Ulcerative Colitis Human Sigmoid Colon

“…Sample preparation and neurokinin A radioimmunoassay were performed as described previously (Lindstrom and Andersson, 1997;Grider, 2003) with minor modification. After equilibration, the muscle strips were rinsed three times with fresh Krebs' solution.…”

Interactive contribution of NK1 and kinin receptors to the acute inflammatory oedema observed in response to noxious heat stimulation: studies in NK1 receptor knockout mice

“…(1995) reported that plasma extravasation and substance P release was suppressed in burn wounds in kininogen‐deficient rats. Furthermore, in other models of experimental inflammation, it has been reported that inducible B 1 (Ferreira et al ., 2000) and constitutive B 2 receptors (Ricciardolo et al ., 1994; Lindstrom & Andersson, 1997; Schuligoi et al ., 1998) mediate tachykinin release from afferent sensory neurons. Taken together, we conclude that a similar interaction may occur in thermally injured tissues.…”

“…However in NK 1 receptor knockout mice, the kinin antagonists were without effect (Cao et al ., 2000). Indeed, evidence for a link between the tachykinin and kinin receptors has been produced in several models of inflammation (Ricciardolo et al ., 1994; Lindstrom & Andersson, 1997; Schuligoi et al ., 1998; Ferreira et al ., 2000). In addition, studies in the microvasculature of neutral endopeptidase knockout mice have revealed that spontaneous plasma leakage is inhibited by treatment with NK 1 and kinin B 2 antagonists (Lu et al ., 1997).…”