Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 433

Table 8.19. Direct vasoconstrictors that activate GPCRs. ( Part 1 ) Gi/o-coupled receptors.
G-protein-coupled receptors on vascular smooth myocytes can generate a vasoconstriction upon
ligand binding (Source: [ 812 ]). Among these, some receptors are linked to several signaling cas-
cades via different G-protein subunits — G α 12 / 13 — that inhibit adenylate

cyclase and activate phospholipase-C and monomeric GTPase Rho, respectively. Activation of
members of the subclass of G

α i / o ,G α q / 11 , and/or G

α i / o subunits inhibits adenylate cyclase, but stimulates via G βγ

phospholipase-C, hence cau sing Ca 2 + influx.

GPCR Type Agonist

α 2a/2b/2c Adrenaline

5HT 1B Serotonin

A 1 Adenosine

P2Y 12 ADP

APJ Apelin

ETB Endothelin-1

NK 2 Neurokinin-A

Y 1 Neuropeptide-Y

Sst 2 Somatostatin

EP 3 Prostaglandin-E2

BLT 1 Leukotriene-B4

S1P 2 / 3 Sphingosine 1-phosphate

PA R 1 Thrombin

beds as well as between arterial and venous and central and peripheral blood vessels
[ 812 ]. Vasoactive substances encompass nucleotides and -sides, acetylcholine,
biogenic amines and other peptides, eicosanoids, and lipid messengers.

Eicosanoids

Eicosanoids (or icosanoids) include prostaglandins, prostacyclins, thromboxanes,
leukotrienes, and lipoxins (Tables 8.24 to 8.26 ). Leukotrienes regulate smooth
muscle tone, hence wall permeability, as well as cell adherence and chemotaxis.
Endothelial cells cannot synthesize leukotrienes, but cooperate with neutrophils to
metabolize leukotrienes.
Prostacyclin is synthesized by endothelial cells in response to inflammatory
mediators. Cultured endothelial cells metabolize arachidonic acid not only to
prostaglandins, but also to hydroxyeicosatetraenoic acids (HETE) and epoxye-
icosatrienoic acids (EET; Fig. 8.3 ). In the presence of EETs and DHETs, isolated
porcine coronary arteries relax.
Leukotrienes are local messengers generated primarily in leukocytes. Activated
cytosolic phospholipase-A2 liberates arachidonic acid from membrane phospho-
lipids. 5-Lipoxygenase interacts with 5LOx-activating protein (FLAP), or arachido-
nate 5LOx-activating protein (ALOx5AP), that facilitates the recruitment of transfer
of arachidonic acid to 5LOx [ 815 ]). (1) At the nuclear envelope, incorporation