Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 761

12.3.3 Regulation of Mucus Secretion

Submucosal glands continuously secrete polymeric mucins at a low level. They
can be further stimulated by adrenergic, cholinergic, and non-adrenergic, non-
cholinergic nervous signals (Sect. 12.3.1.4 ). Therefore, 2 secretion mechanisms
exist. The basal secretion at low level is unregulated. It is carried out by continuous
movement of secretory granules driven by the cytoskeleton. The regulated secretion
corresponds to granule exocytosis in response to extracellular stimuli to increase
mucus secretion. Mucus secretion is elicited by irritations, such as dust and smoke.
The secretion of polymeric mucins is regulated separately from mucin produc-
tion [ 1545 ]. Many mediators trigger mucin secretion, such as cholinergic agonists
(also called parasympathometic agents), lipid mediators, oxidants, cytokines, neu-
ropeptides, neutrophil elastase, ATP and UTP, etc. On the other hand, interleukin-4,
-9, and -13 provoke mucin synthesis.
Muscarinic M 3 receptors are detected on airway smooth myocytes as well as
submucosal glands, whereas M l and M 2 receptors are located in parasympathic
ganglia and cholinergic nerves in lungs, respectively. Receptor M l is also observed
in submucosal glands.
In humans, adrenergic nerves of airways could stimulate mucus secretion via

α -Agonists stimulate ciliary beating in a dose-dependent

fashion. A third component of the autonomic nervous system of lungs, the non-
adrenergic, non-cholinergic nervous component represents the single inhibitory
nervous mechanism in humans. Vasoactive intestinal peptide in conjunction with
peptide histidine methamine serves as neurotransmitter. It not only increases fluid
transport across the epithelium and mucin secretion, but also can inhibit resting
secretion of mucus. It raises cAMP concentration in submucosal glands, respiratory
epithelium, and airway smooth muscle.
Substance P and calcitonin gene-related peptide are colocalized in afferent nerves
of human airways. They contract airway smooth myocytes, elevate mucus secretion,
and can provoke mucosal edema. Histamine, leukotrienes, and prostaglandins PGa2
and PGf2 also augment airway mucus secretion.
The most important secretagogue in the respiratory epithelium is ATP that binds
to P2Y 2 receptors [ 1545 ]. Other messengers, such as acetylcholine and histamine,
may directly activate receptors on airway epithelial cells or cause airway smooth
myocyte contraction, thereby leading to ATP release.
Airway surface liquid hydration, hence effective mucin dispersion into airway
surface liquid volume, requires electrolytes and water secretion onto the wetted
respiratory surface. Therefore, mucin secretion rate must match ion and water
transfer fluxes.
The volume of the airway surface liquid layer depends on the amount of Na + and
Cl − in the airway lumen, hence of Na + absorption by epithelial Na + channel and
Cl − secretion by the Ca 2 + -activated Cl − channel and cystic fibrosis transmembrane

-and β -adrenoreceptors. β