Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 760

Table 12.2. Tachykinins receptors in cells of the respiratory tract (Source: [ 1544 ]).

Target cell Tachykinin receptor types

Postganglionic nerves NK 1 ,NK 2 (between-species variability)

Tracheobronchial ganglia NK 1 ,NK 2

Airway epithelial cell NK 1

Alveolar macrophage NK 2

Airway smooth myocyte NK 2

Seromucous glands NK 1

Pulmonary endothelial cell NK 1

Pulmonary smooth myocyte NK 2

Postcapillary venule NK 1

as well as in perfused tracheal arteries of anesthetized dog, possibly preceded by
transient vasoconstriction. They can thus have a mixed effects on the pulmonary
and bronchial circulations. Tachykinins also raise airway mucosa microvascular
permeability. Last, but not least, these powerful secretagogues stimulate ciliary
beating in synergy with mucus secretion.

12.3.2 Mucus Release

Mucins are stored in a dehydrated form in secretory granules. Exocytosis is executed
in 3 main steps: (1) motion of mucin granules to the apical plasma membrane;
(2) fusion with the plasma membrane; and (3) opening onto the airway surface.
Each calcium counterion within the granule is exchanged for 2 sodium ions in the
extracellular space [ 1545 ]. Rapid secretion enables the formation of concentrated
mucus that is resistant to dilution once the mucin network is formed.
Step 1 is regulated by myristoylated alanine-rich C-kinase substrate (MAR-
CKS) [ 1546 ]. Activated protein kinase-C phosphorylates MARCKS, causing MAR-
CKS translocation from the plasma membrane to the cytoplasm. Agent MARCKS
is then dephosphorylated by protein phosphatase PP2 that is activated by cGMP-
dependent protein kinase PKG, itself stimulated by the NO-cGMP pathway. A
cooperative interaction between protein kinases PKC and PKG is then required.
Dephosphorylated cytoplasmic MARCKS associates with the contractile cytoskele-
ton (Vol. 1 - Chap. 6. Cell Cytoskeleton). Step 2 probably implicates a coordinated
interaction between soluble N ethylmaleimide-sensitive factor receptors (SNARE),
MUnc13-4, 13 and small GTPase Rab.

13 MUnc13-4 is a protein expressed in lungs by goblet cells and by alveolar cells 2 [ 1547 ].