Biology Reference
In-Depth Information
In a mouse model of asthma, we observed no influence of the tachykinin NK
1
recep-
tor on the development of allergic airway inflammation. However, allergen-induced
goblet cell hyperplasia, one of the features of airway remodeling, was decreased in
mice lacking the tachykinin NK
1
receptor
[122]
.
So, from animal studies, it seems that both the tachykinin NK
1
and NK
2
receptors
are involved in antigen-induced airway effects. In addition, it is possible that tachykinin
NK
3
receptors are involved in this process: administration of the tachykinin NK
3
recep-
tor antagonist SR-142801 via aerosol caused a significant reduction in neutrophil and
eosinophil influx in the airways of ovalbumin-sensitized and -challenged mice
[123]
.
In animal models, tachykinins and their receptors have been shown to be involved
in airway responses to nonspecific stimuli. Both the NK
1
and the NK
2
tachykinin
receptors have been found to be involved in airway contraction induced by cold
air
[124,125]
, hyperventilation, and cigarette smoke
[126]
; in plasma extravasation
induced by hypertonic saline
[127,128]
; and in airway hyperresponsiveness induced
by viruses
[129]
, IL-5, and nerve growth factor
[130,131]
. In addition, the tachykinin
NK
3
receptor was found to be involved in citric acid-induced cough and enhanced
bronchial responsiveness
[77]
. From studies performed in tachykinin NK
1
receptor
knockout mice, it is becoming apparent that the tachykinin NK
1
receptor plays a role
in cigarette smoke-induced airway inflammation
[132]
.
9.5 Conclusions
The tachykinins substance P and neurokinin A are present in human airways, in sensory
nerves and immune cells. Tachykinins can be recovered from the airways after inhala-
tion of ozone, cigarette smoke, or allergens. They interact in the airways with tachykinin
NK
1
, NK
2
, and NK
3
receptors to cause bronchoconstriction, plasma protein extrava-
sation, and mucus secretion, and to attract and activate immune cells. In preclinical
studies, they have been implicated in the pathophysiology of asthma, including allergen-
and cigarette-smoke-induced airway inflammation and bronchial hyperresponsive-
ness. Clinical studies with potent tachykinin receptor antagonists (such as the recently
described dual NK
1
/NK
2
or triple NK
1
/NK
2
/NK
3
tachykinin antagonists
[133,134]
)
should permit a definite judgment on their importance in allergic airway diseases.
References
1. Richardson JD, Vasko MR. Cellular mechanisms of neurogenic inflammation. J Pharmacol
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2. Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilatation
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310:175-83.
3. Barnes PJ. Neurogenic inflammation in the airways. Respir Physiol 2001;125:145-54.
4. Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V. The tachykinin
peptide family. Pharmacol Rev 2002;54:285-322.
