Modulatory role of tachykinin NK<sub>1</sub>receptor in cholinergic contraction of mouse trachea

Tournoy, Kurt G.; Swert, Katelijne O. De; Leclere, Pascal; Lefebvre, R.A.; Pauwels, R.; Joos, Guy

doi:10.1183/09031936.03.00007803

Cited by 22 publications

(21 citation statements)

References 33 publications

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“…Moreover, the NK-1 receptor antagonist attenuated the effects of the estrogen receptor antagonist in enhancing AHR in female mice in vivo. NK1 receptor stimulation has been shown to augment cholinergic neurotransmission in mouse trachea when in vitro airway responsiveness was detected by EFS (36). Thus, these data support the notion that the rapid onset of estrogen regulation of smooth muscle contractility is NK-1-dependent and involves prejunctional activation but does not interfere with cholinergic airway smooth muscle constriction.…”

Section: Discussionsupporting

confidence: 77%

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Matsubara

Swasey

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et al. 2008

Am J Respir Cell Mol Biol

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The female hormone estrogen is an important factor in the regulation of airway function and inflammation, and sex differences in the prevalence of asthma are well described. Using an animal model, we determined how sex differences may underlie the development of altered airway function in response to allergen exposure. We compared sex differences in the development of airway hyperresponsiveness (AHR) after allergen exposure exclusively via the airways. Ovalbumin (OVA) was administered by nebulization on 10 consecutive days in BALB/c mice. After methacholine challenge, significant AHR developed in male mice but not in female mice. Ovariectomized female mice showed significant AHR after 10-day OVA inhalation. ICI182,780, an estrogen antagonist, similarly enhanced airway responsiveness even when administered 1 hour before assay. In contrast, 17b-estradiol dose-dependently suppressed AHR in male mice. In all cases, airway responsiveness was inhibited by the administration of a neurokinin 1 receptor antagonist. These results demonstrate that sex differences in 10-day OVAinduced AHR are due to endogenous estrogen, which negatively regulates airway responsiveness in female mice. Cumulatively, the results suggest that endogenous estrogen may regulate the neurokinin 1-dependent prejunctional activation of airway smooth muscle in allergen-exposed mice.Keywords: estrogen; sex; airway hyperresponsiveness; EFS; neuronal activation Sex differences have been described to play a role in various diseases, including atherosclerosis (1), osteoporosis (2), and certain neurologic disorders (3). Accumulating evidence suggests that hormonal factors are important in the expression of such sex differences at the phenotypic and genotypic levels. A number of epidemiologic and experimental reports suggest that the female hormone estrogen is an important factor in the regulation of airway function and inflammation. Estrogen can prevent cholinergic constriction of asthmatic tracheal rings in vitro (4), and estrogen treatment decreases airway responsiveness to acetylcholine in ovariectomized rats (5). On the other hand, female mice may be more susceptible than male mice to allergen-induced airway inflammation (6-8). The role of estrogen on sex differences in asthma has been the subject of much discussion (9, 10).There are many animal protocols for investigating allergeninduced airway hyperresponsiveness (AHR) and inflammation, with the majority using initial sensitization to allergen together with an adjuvant such as alum. Using this sensitization approach, some mouse studies have suggested a female superiority in the development of allergic airway inflammation (6-8). We examined the development of AHR after allergen exposure exclusively via the airways for 10 consecutive days in the absence of any adjuvant. Although AHR to inhaled methacholine (MCh) was not detected in female mice after 10-day ovalbumin (OVA) inhalation in vivo, electrical field stimulation (EFS) in vitro detected altered airway responsiveness. In large part, this EFS respon...

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Section: Discussionsupporting

confidence: 77%

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Matsubara

Swasey

Loader

et al. 2008

Am J Respir Cell Mol Biol

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“…These peptides may in turn mediate a relaxation through binding with the epithelium and subsequent release of prostaglandin, as was described in vitro. 34 Exogenous substance P indeed has an inhibitory effect on carbacholinduced bronchoconstriction in NK 1 receptor WT mice. This inhibition was abolished in the NK 1 receptor knockout mice, suggesting that this protective effect is mediated through the NK 1 receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Altered smooth muscle contractility to carbachol in the NK 1 receptor knockout animals does not seem to be the cause, either. 34 On sensory nerve activation (through contraction), an antidromic release of tachykinins from c-fibers via an axon reflex may occur. These peptides may in turn mediate a relaxation through binding with the epithelium and subsequent release of prostaglandin, as was described in vitro.…”

Section: Discussionmentioning

confidence: 99%

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

Swert

Tournoy

Joos

et al. 2004

Journal of Allergy and Clinical Immunology

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Background: Tachykinins are present in sensory nerves and in nonneuronal cells like macrophages. Human data suggest a role for these peptides in asthma, but the exact role of tachykinins and their receptors in allergic airway inflammation is still a matter of debate. Objective: The aim of this study was to determine the role of the tachykinin NK 1 receptor in allergic airway responses in a mouse model. Methods: Tachykinin NK 1 receptor wild-type and knockout animals were sensitized intraperitoneally to ovalbumin and subsequently exposed from days 14 to 21 to aerosolized ovalbumin (1%). On day 22, the immunologic and histologic changes were evaluated, and lung function measurements were performed. Results: Mice lacking the tachykinin NK 1 receptor and their wild-type litter mates developed inflammatory cell infiltrates in the airways and ovalbumin-specific IgE on sensitization and exposure to ovalbumin compared with saline-exposed controls. No differences were detected between wild-type and knockout mice. The substance P content of alveolar macrophages was not influenced by ovalbumin or by the lack of the NK 1 receptor. Ovalbumin-induced hyperresponsiveness was not observed, but at baseline, the knockout mice were more reactive despite similar morphology. Ovalbumin induced more goblet cell hyperplasia in wild-type animals compared with knockout animals. No differences in airway wall thickness were observed. Conclusion: These data suggest that tachykinin NK 1 receptors do not affect allergic airway inflammation or endogenous substance P content of alveolar macrophages but influence baseline responsiveness and promote features of remodeling such as goblet cell

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“…HT between the tachykinin NK 1 receptor WT and KO mice is not very likely since there were no longer differences between the contractile responses of both groups to 5-HT in the presence of atropine or TTX. Furthermore, we previously showed that the tracheal smooth muscle preparation of the WT and KO mice respond similar to the cholinergic agonist carbachol [23]. A generalized artifact of cholinergic nerve activity seems unlikely too, since electrical field stimulation of the tracheas from NK 1 receptor knockout animals still generated acetylcholine release and acetylcholine-mediated contraction although this release and contraction were diminished compared to the response in the WT counterparts [23].…”

Section: Discussionmentioning

confidence: 99%

“…The contractions were measured isometrically with Grass FT03 transducers (Grass Instruments Co., Quincy, MA, USA) and recorded on a Graphtec Linearecorder type WR3701 (Graphtech corp. Tokyo, Japan). Contractions were expressed as percent of the contraction that was observed using a maximal concentration of carbachol, as tracheas of both tachykinin NK 1 receptor WT as KO animals were shown previously to respond similarly to carbachol [23].…”

Section: Micementioning

confidence: 99%

Role of the tachykinin NK1 receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea

Swert

Lefebvre

Pauwels

et al. 2007

Pulmonary Pharmacology & Therapeutics

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Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Cited by 22 publications

References 33 publications

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

Role of the tachykinin NK1 receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea

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Modulatory role of tachykinin NK1receptor in cholinergic contraction of mouse trachea

Cited by 22 publications

References 33 publications

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

Estrogen Determines Sex Differences in Airway Responsiveness after Allergen Exposure

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

Role of the tachykinin NK1 receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea

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Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea