Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 344

Table 6.24. Adrenergic receptors; corresponding signaling pathways; and functions in nervous,
cardiac, and vascular tissues (Source: [ 650 ]). Effectors include adenylate cyclase (ACase),
cyclic adenosine monophosphate (cAMP), protein kinase-A (PKA), guanylate cyclase (GCase),
cyclic guanosine monophosphate (cGMP), protein kinase-G (PKG), nitric oxide synthase (NOS),
phospholipase-C (PLC), diacylglycerol (DAG), inositol trisphosphate (IP 3 ), calcium ions, protein
kinase-C (PKC), phosphoinositide 3-kinase (PI3K), phosphoinositide-dependent kinase-1 (PDK1),
prote in kinase-B (PKB), Rho GTPase, and mitogen-activated protein kinases (MAPK).
Receptor

Effectors Functions

Gq-PLC-IP 3 -Ca 2 + α 1a Inotropy + ,

Rho-RoCK myocyte growth,

MAPK (ERK, JNK, P38MAPK) vasoconstriction

Gq-PLC-IP 3 -Ca 2 + α 1b Inotropy + ,

ERK, P38MAPK myocyte growth,

vasoconstriction

Gq-PLC-IP 3 -Ca 2 + α 1d Vasoconstriction

MAPK (weakly)

α 2a Gi Sympathetic output

(presynaptically) reduction, hypotension

α 2b Gi α 2a counteraction,

(postsynaptically) peripheral vasoconstriction,

hypertension

α 2c Gi Sympathetic output

(presynaptically, reduction,

at low frequency nerve activity) cAMP antagonist

(postsynaptically) Vasoconstriction (cold),

hypotension

β 1 Gs-ACase-cAMP-PKA Inotropy + , lusitropy + ,

metabolism, growth

β 2 Gs-ACase-cAMP-PKA Inotropy + , lusitropy + ,

Gi/G βγ -PLC-DAG-PKC metabolism, growth,

G βγ -PI3K-PDK1-PKB CMC survival,

relaxation of bronchial
and vascular SMC

β βγ −

3 Gi/G -PLC-DAG-PKC Inotropy ,

Gi/G βγ -NOS-NO-GCase-cGMP-PKG CMC survival

q , which signals via phospholipase-
C leading to: (1) diacylglycerol, then activating protein kinase-C; and (2) ino-
sitol trisphosphate and calcium influx mainly from the sarcoplasmic reticulum.
α

Activated α 1-adrenoceptors interact with G α

α i inhibit plasmalemmal adenylate cyclase, 82

2-Adrenoceptors coupled to G ac-

tivating K + channels and inhibiting sarcolemmal Ca V 1 channels.

82 Among the 9 known isoforms (ACase1-ACase9), adenylate cyclase-5 is specifically expressed
in cardiomyocytes; adenylate cyclase-6 is expressed in other cardiac cells. Other isoforms are
expressed in the heart to a lesser extent. The fine-tuning in ACase regulation controls the adrenergic