Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 382

Ca

VDCC

MLC

ATP

Cam

Ca

+

MLCK Pase

Ca Cam

ADP

−

MLC−P

PKC

− RoK

Cdm

actomyosin interactions

ATn2 IP3 + DAG

+

R

Ca

+

PLC

+

−

ET−1

G

PIP2 cAMP

GPCR

ETR−A

Gi

−

+ Ca

ACase

+

Gs

NAd ATP

SR

Ad

α

β

PKG

+

GTP cGMP

+

K

GCase

NO

Fig. 8.1 The smooth myocyte function and its regulation (Source: [ 761 ]). Two pathways are
involved: (1) the phosphatidylinositol and (2) Gs-protein axes. A ligand activates a GPCR, which
stimulates phospholipase-C (PLC), producing inositol trisphosphate (IP 3 ) and diacylglycerol
(DAG) from phosphatidylinositol bisphosphate (PIP 2 ). IP 3 releases calcium from the sarcoplas-
mic reticulum (SR) and DAG activates protein kinase-C (PKC). PKC acts on the contractile
proteins and ion channels. Calcium and calmodulin (Cam) stimulate a myosin light chain kinase
(MLCK), leading to actin-myosin interactions. Noradrenaline (NAd), acting via 1-adrenoceptors,

angiotensin-2 (ATn2) via its cognate receptors, and endothelin-1 (ET1) via ETRa receptors (ET A ;
in fugure ETR-A) activate phospholipase-C (PLC). Gs protein activated by a

α

2-adrenoceptor
agonist stimulates adenylate cyclase (ACase), which catalyzes the formation of cAMP messenger.
The latter inhibits MLCK and causes vasodilation.

β

Calmodulin isoforms (Cam1-Cam3) are encoded by 3 genes in humans. In ad-
dition to these isoforms, the calmodulin family contains calmodulin-like proteins
(CalmL1 and CalmL3-CalmL6) 6

6 Calcium-binding calmodulin-like protein-3 is also called calmodulin-like protein (CLP), CalmL5
calmodulin-like skin protein (CLSP), and CalmL6 calglandulin-like protein (CalgP or CagLPL).