Biomedical Engineering Reference
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micromolar concentrations of ATP and prostaglandin-F2
[
1579
]. Ciliostimulator
ATP acts via nucleotide receptors that are coupled to plasmalemmal calcium
channels, whereas PGf2
α
releases Ca
2
+
from its intracellular store.
Adenosine reduces intracellular cAMP content and ciliary beat frequency in
cultured rabbit tracheal epithelium [
1580
]. Adenosine A
2
-receptor agonist acts only
slightly on ciliary activity, whereas adenosine A
1
-receptor agonist attenuates the
ciliary beat frequency in a dose-dependent fashion. Adenosine A
1
-receptor inhibits
adenylate cyclase and impairs respiratory ciliary activity. Conversely, adenosine
receptor antagonist 8-phenyltheophylline reverses the effect of adenosine on cAMP
level and ciliary beat frequency. On the other hand, adenosine-induced activation
of apical receptor A
2B
primes PLC-Ca
2
+
signaling that stimulates basolateral
Ca
2
+
-activated K
+
channels and contributes substantially to anion secretion [
1581
].
Hence, apical adenosine activates: (1) contralateral K
+
channels via the PLC-Ca
2
+
axis for transepithelial anion secretion in coordination with (2) ipsilateral cystic
fibrosis transmembrane conductance regulators via the cAMP-PKA axis. It then
causes secretion of both chloride and bicarbonate.
Neurokinin-A augments the ciliary beat frequency via tachykinin receptors in
cultured rabbit tracheal epithelium [
1582
]. Substance-P does not significantly affect
the airway ciliary activity. However, neutral endopeptidase inhibitor potentiates
substance-P response, but not that of neurokinin-A. Other peptidase inhibitors do
not alter tachykinin-induced increase in ciliary beat frequency.
28
Angiotensin-2 elevates the ciliary beat frequency [
1583
]. Ciliostimulator
angiotensin-2 targets its cognate receptors to provoke a prostaglandin action without
changing intracellular cAMP level.
Other regulators, such as cGMP, protein kinases PKG and PKC, calmodulin,
phospholipase-C, and nitric oxide influence ciliary beating (Table
12.6
). Human
ciliary beat disappears in vitro at a temperature of 4
◦
C. Above this threshold, protein
kinase-C and Ca
2
+
-calmodulin-dependent kinase CamK2 regulate nasal ciliary beat
frequency in response to rising temperature [
1584
].
Exhaled nitric oxide is produced mainly in paranasal sinuses and nasal mucosa.
Nasal nitric oxide can serve as an anti-infectious agent in the nose and associated
sinuses and contributes to the mucociliary clearance. Nitric oxide production
by inducible nitric oxide synthase is enhanced in nasal epithelium of patients
with allergic rhinitis. Inducible nitric oxide synthase (NOS2) is upregulated in
respiratory epithelium excited by tumor-necrosis factor-
α
and lipopolysaccharides.
Baseline ciliary activity depends on NO production [
1585
]. In addition, at very
low concentration (1-10 mmol), alcohol stimulates ciliary motility by rapidly and
sequentially activating the NOS3-NO-GC-cGMP-PKG axis and soluble adenylate
cyclase signaling (sAC-cAMP-PKA pathway) [
1586
]. However, long-term, heavy
alcohol consumption disturbs mucociliary clearance and nitric oxide signaling in
ciliated epithelial cells.
α
28
Therefore, angiotensin-converting enzyme, aminopeptidases, and serine peptidases do not
modulate ciliary activity in response to tachykinins [
1582
].
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