Biology Reference
In-Depth Information
9
Role of Tachykinins in Asthma
and Allergic Disease
Katelijne O. De Swert, Guy F. Joos
Department of Respiratory Medicine, Laboratory for Transitional
Research in Obstructive Pulmonary Diseases, Ghent University
Hospital, Ghent, Belgium
9.1 Introduction
The inflammation that results from the release of substances from primary sensory
nerve terminals is called
neurogenic inflammation.
More than 100 years ago, the
first observations were made that activation of dorsal root ganglia neurons results
in vasodilation. Since then, abundant evidence has been accumulated to suggest that
activation of peripheral terminals of sensory neurons by local depolarization, axonal
reflexes, or dorsal root reflexes releases bioactive substances. These substances
act on target cells in the periphery, such as mast cells, immune cells, and vascular
smooth muscle cells, to produce inflammation (redness and warmth, swelling, and
hypersensitivity)
[1]
.
Small-diameter sensory neurons that are sensitive to capsaicin are of major impor-
tance in the generation of neurogenic inflammation. The neuropeptides substance P
and calcitonin gene-related peptide (CGRP) are considered to be the major initiators
of neurogenic inflammation
[2,3]
. Substance P and neurokinin A are member of the
tachykinin peptide family and are potent vasodilators and contractors of smooth mus-
cle
[4]
. In studies on rodent airways, substance P and neurokinin A have been impli-
cated as the neurotransmitters mediating the excitatory action of the nonadrenergic/
noncholinergic (NANC) nervous system. These noncholinergic excitatory nerves can
be activated by mechanical and chemical stimuli, generating antidromic impulses and
a local axon reflex that leads to noncholinergic bronchoconstriction and neurogenic
inflammation
[5,6]
.
Substance P and neurokinin A have various effects that could contribute to the
changes observed in the airways of patients with (allergic) asthma. These include
smooth muscle contraction, submucosal gland secretion, vasodilation, increase in
vascular permeability, stimulation of cholinergic nerves, stimulation of mast cells,
stimulation of B and T lymphocytes, stimulation of macrophages, chemoattraction of
eosinophils and neutrophils, and the vascular adhesion of neutrophils. This chapter
discusses the role of tachykinins and their receptors in allergic airway inflammation.
