Role of Tachykinins in Asthma and Allergic Disease - New Insights to Neuroimmune Biology - page 169

of G proteins [72] . Lower concentrations caused mast-cell activation by interac-
tion with tachykinin receptors. The histamine release from a murine mast-cell line
is mediated by tachykinin NK 2 receptors [73] , whereas the mast-cell degranulation
induced by substance P in Fisher 344 rat airways involved tachykinin NK 1 receptors
[61,74] .
9.3.2 Cough
An afferent (sensory) arm and an efferent arm that synapses in the brainstem areas,
including the nucleus tractus solitarius, make up the reflex arch that mediates the
cough reflex. Mediators and mechanisms of the sensory arm of this reflex path-
way are not completely understood, though pharmacological evidence exists for the
involvement of substance P [75,76] . The role of tachykinins in the regulation of the
cough response appears to be complex, as antagonists for the three tachykinin recep-
tors have antitussive activity in preclinical models [77-79] . In guinea pigs, substance
P locally applied into the airways has been shown to produce [80] or potentiate
cough produced by other stimuli [79] . These findings support a role for substance P
at a peripheral site of action, but central sites of action have also been reported [81] .
9.3.3 Secretion of Mucus, Water, and Electrolytes
Relatively strong evidence exists that tachykinins released from sensory nerve fibers
are physiological (and pathological) regulators of secretion in the upper and lower
airways. A local release of tachykinins in the nasal mucosa could play a role in the
defensive response to irritants. Intranasally administered capsaicin-induced sneezing,
pain, and nasal secretion in both experimental animals and humans [82] . Similarly,
local tachykinin administration evoked secretion. In the lower tracheobronchial tree,
seromucous glands and goblet cells produce mucus. Both sources are under neural
control. Depending upon species and airway level, innervation comprises parasym-
pathetic, sympathetic, and “sensory-efferent” pathways [83] . The transmitters of
the latter pathway are substance P and neurokinin A, which act via tachykinin NK 1
receptors [84,85] . Recently, an involvement of tachykinin NK 3 receptors in porcine
airways has been suggested [85] . However, compared to cholinergic control, the
excitatory nonadrenergic/noncholinergic (eNANC) neural control of human airway
secretion appears to be a minor component [83] . Mucus secretion is closely coupled
to liquid secretion to ensure optimal ciliary transport and presence of adequate con-
centrations of antibacterial substances on the airway surface. Substance P has also
been shown to be involved in this process in porcine airways [86] .
9.3.4 Alveolar Epithelial and Microvascular Permeability
The involvement of sensory nerves in producing increased vascular permeability and
plasma extravasation was first described in skin and conjunctiva and termed neuro-
genic inflammation [87] . Neurogenic inflammation has also been described in the