Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 759

glucagon-like peptides GLP1 and GLP2, 9 glucose-dependent insulinotropic peptide
(GIP), and growth hormone-releasing hormone (GHRH). 10 Vasoactive intestinal
peptide is coproduced with peptide histidine methionine. Vasoactive intestinal
peptide modulates cholinergic transmission in airways. In addition, the coexistence
of VIP and substance-P in cholinergic nerves of airways yields a balance between
the bronchoconstrictory, pro-inflammatory substance-P and the bronchiorelaxant,
anti-inflammatory VIP [ 1544 ]. 11 Moreover, VIP and NO cooperate to relaxing
airway and vascular smooth myocytes. Nitric oxide acts as a cotransmitter of
non-adrenergic non-cholinergic (NANC) relaxation. Vasoactive intestinal peptide,
directly or by interacting with other transmitters such as acetylcholine, stimulates
airway secretion and ciliary mobility.
Pituitary adenylate cyclase-activating polypeptide AdCyAP1 can be observed
in nerves around tracheal and bronchial smooth muscle, glands, and blood ves-
sels [ 1544 ]. It coexists with the neuropeptides calcitonin gene-related peptide and
substance-P.
Tachykinin nerves feed airways. Tachykinins are synthesized in the neuronal

bodies of a subset of sensory neurons in dorsal root ganglia. Tachykinin

+

nerves
distribute to the tracheobronchial epithelium, lamina propria, and smooth muscle,
as well as to alveolar walls, systemic and pulmonary blood vessels, and airway
ganglia [ 1544 ]. Inflammation is triggered by tachykinin release from nerve end-
ings. Stimuli of tachykinin liberation in airways include bradykinin 12

+

and various

prostanoids.
The tachykinin family includes substance-P, neurokinin-A (substance-K) and -
B (neuromedin-K), and neuropeptide-K (neurokinin-K) and -

.TheTAC1and
TAC3 genes encode the tachykinin precursors preprotachykinin-A and -B. The
TAC1 gene (or TAC2) generates multiple splice variants: substance-P, neurokinin-
A, neuropeptide-K, and neuropeptide-

γ

. The TAC3 gene encodes neurokinin-B. The
primary afferent neurons that produce tachykinins and innervate airways express the
TAC1 gene [ 1544 ].
In airways, tachykinins coexist with calcitonin gene-related peptide, a potent
vasodilator. Tachykinins pertain to the most powerful spasmogens on airway
smooth myocytes. Substance-P and neurokinin-A target preferentially NK 1 and
NK 2 receptors (Table 12.2 ).
In human isolated airways, neurokinin-A is more potent than substance-P in
causing long-lasting contraction [ 1544 ]. On the other hand, tachykinins provoke
endothelium-dependent vasodilation of isolated precontracted pulmonary arteries

γ

9 Glucagon results from the cleavage of proglucagon in pancreatic islet

β cells. In intestinal L cells,

proglucagon is split into glicentin, GLP1, and GLP2 peptides.
10 A.k.a. growth hormone-releasing factor (GRF or GHRF), somatoliberin, and somatocrinin.
11 Vasoactive intestinal peptide represses the broncho- and vasoconstrictor effect of histamine,
prostaglandin-F2 , leukotriene-C4 and -D4, neurokinin-A and -B, and endothelin. It reduces

platelet-activating factor (PAF)-induced edema.
12 Tachykinins are characterized by a fast onset of action, unlike slower acting bradykinins.

α