Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 343

Table 6.23. Sympathetic ( β ) neurotransmitters, receptors and effectors (see caption of Table 6.22 ;

Source: [ 650 ]).

Sympathetic ( β )

Neurotransmitter Noradrenaline

GPCR β 1 β 2 β 3

G Protein Gs Gs Gs

Gi/G βγ Gi/G βγ

βγ

Gq/G

First effectors ACase( + /− ) ase( + /− ) ase( + /− )

PLC PLC

NO/GCase NO/GCase

PI3K PI3K

Second messengers cAMP cAMP cAMP

IP 3 /Ca/DAG IP 3 /Ca/DAG

RNOS/cGMP RNOS/cGMP

PDK1 PDK1

Protein kinases PKA PKA,PKB, PKA,PKB

PKC,PKG PKC,PKG

Effectors Ras, MAPK

Adrenergic G-Protein-Coupled Receptors

The myocardial systolic and diastolic function are mainly governed by β 1- and β 2-

adrenergic receptor activities. However, -adrenergic receptors leads to positive and

negative inotropy. The family of adrenergic receptors consists of 9 subtypes (

α

α 1a-

70%), 79

α 1b, 1%; Table 6.24 ).

Dimerization can occur between adrenergic receptors, such as between

α 1d, α 2a- α 2c, β 1( ∼ β 2( ∼ 10%), and β 3( ∼

α 2- and

β 2-adrenergic receptors. Scaffold A-kinase-anchoring proteins interact with

adrenergic receptors, especially

1- or β

2-adrenoceptors.
Stimulated adrenergic receptors activate pathways leading to cytosolic protein
Ser/Thr kinases (PKA, PKB, PKC, and PKG). 80 Adrenergic G-protein-coupled
receptors can also activate Ras GTPase and MAPK cascades. Phosphorylation by
G-protein-coupled receptor kinases, with arrestin and adaptor AP2, desensitizes
nervous signaling. 81

β

79

1-Adrenergic receptors are downregulated in hypertrophic and ischemic cardiomyopathy.
80 Inactive PKA binds to cAMP, then dissociates into cAMP-bound dimer and active PKAs.
PKC family members are activated via phospholipase-C. PKC

β

α ,PKC β 1/2, and PKC γ require

a phospholipid, Ca 2 + , and DAG for activation; PKC

δ ,PKC ,PKC η ,andPKC θ needs DAG but

not Ca 2 + ;PKC do not have Ca 2 + - and DAG-binding sites.

81 Kinases GRK2 and GRK5 are expressed in cardiomyocytes.

ζ and PKC λ