Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 385

8.3.2 Arachidonic Acid

Arachidonic acid stimulates ATPase activity of unphosphorylated smooth muscle
myosin, heavy meromyosin, and subfragment S1, thereby causing contraction of
smooth myocytes [ 715 ].

8.3.3 G-Protein-Coupled Receptors

In smooth myocytes, signaling from G-protein-coupled receptors controls
contraction and growth as well as tissue remodeling and inflammation. Gq-coupled
receptors that hydrolyzes phosphatidylinositol

(4,5)-bisphosphate into intracellular messengers diacylglycerol and inositol (1,4,5)-
trisphosphate.
Cytosolic Ca 2 + concentration increases upon the release from sarcoplasmic
reticulum stores through IP 3 receptors and influx from plasmalemmal IP 3 channels
(Vol. 3 - Chap. 3. Main Classes of Ion Channels and Pumps). Elevated intracel-
lular calcium level causes Ca 2 + binding to calmodulin. Calcium-calmodulin then
activates myosin light chain kinase. The latter phosphorylates myosin light chains
to enable actin to activate myosin ATPase activity for contraction of actomyosin
filaments.
Diacylglycerol that remains bound to the plasma membrane initiates the
translocation of protein kinase-C from the cytoplasm to the membrane and its
subsequent activation. Protein kinase-C phosphorylates calponin to relieve its
inhibition of myosin ATPase. It also phosphorylates components of MAPK
modules (Vol. 4 - Chap. 6. Mitogen-Activated Protein Kinase Modules) that
activate transcription factors involved in cell growth. In addition, PKC stimulates
phospholipase-A2 that releases arachadonic acid.
Gq-coupled receptors also interact with guanine nucleotide-exchange factors of
Rho GTPases (RhoGEFs) to regulate actin network reorganization. Monomeric Rho
GTPase activates RoCK kinase that phosphorylates the myosin-binding subunit
of myosin light chain phosphatase to inhibit its activity, thereby heightening
phosphorylation of myosin light chain.

operate via phospholipase-C β

8.3.4 Guanylate Cyclases, Nitric Oxide,

and Natriuretic Peptides

Nitric oxide and atrial natriuretic peptide relax smooth myocytes via soluble and
particulate guanylate cyclases, cGMP messenger and cGMP-dependent protein