Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 397

2-adrenergic receptors cause a bronchorelaxation and inhibit
proliferation of human airway smooth myocytes.

Gs-coupled β

β 2-Adrenoceptors also mediate

vasodilation and influence mucus production and transport and activity of

cholinergic nerves [ 725 ].
Relaxation of airway smooth muscles results from Gs stimulation and subsequent
elevation of intracellular cAMP level and activation of protein kinase-A. The latter
phosphorylates myosin light chain kinase, thereby reducing MLCK affinity for
calcium-calmodulin, myosin phosphorylation, and actin-myosin coupling. Smooth
myocyte relaxation can also result from the decrease in concentration of free
calcium ions. In fact, 2-adrenoceptors operate via cAMP and RapGEF3 and

RapGEF4, 23 but not protein kinase-A [ 726 ].

β

Muscarinic Acetylcholine Receptors

Airway smooth myocytes are innervated by postganglionic parasympathetic nerves
that release acetylcholine. Muscarinic acetylcholine M 2 and M 3 receptors (mAChR)
are coexpressed in many types of smooth myocytes, such as those in walls of blood
vessels and airways.
The density of M 2 receptors is greater than that of M 3 receptors (relative density

≥ 4:1) [ 727 ]. In smooth myocytes, M 2 receptor inhibits AC5 and AC6 adenylate

cyclases via G α i3 , whereas Gq-coupled M 3 activates AC5 and AC6 via G βγ [ 728 ].

In airway smooth myocytes, activated Gi-coupled M 2 receptor inhibits

β -adrenergic-mediated relaxation; activated Gq-coupled M 3 receptor initiates their

contraction. Gq-coupled receptors are the main mediators of contraction of airway
smooth myocytes. Neurotransmitter acetylcholine acts on M 3 receptors to control
the resting tone.

8.4.4.2 Receptor Protein Tyrosine Kinases

Epidermal Growth Factor Family Members

Bronchial epithelial cells produce members of the epidermal growth factor family,
such as EGF, transforming TGF and heparin-binding EGF-like (HBEGF) growth

factors, and amphiregulin, that can stimulate cell migration, proliferation, differen-
tiation, and survival, as well as repair of bronchial epithelia.
Both epidermal (EGF) and heparin-binding EGF-like (HBEGF) growth factor
promote repair of human bronchial epithelial cells [ 729 ].
In normal subjects, the concentration of epidermal growth factor receptor (HER1
or EGFR) is lower than that in asthmatic subjects [ 729 ].Themoreseveretheasthma,
the higher the EGFR level. Agent EGF contributes to hypertrophy and hyperplasia
of airway smooth myocytes during airway remodeling in asthma [ 730 ].

α

23 A.k.a. EPAC1 and -2 as well as cAMPGEF1 and -2, respectively.