Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 342

Table 6.22. ) neurotransmitters, receptors, and effectors.

Protein Gs activates adenylate cyclase (ACase), which triggers the PKA pathway, leading to
positive inotropy (faster, stronger, shorter contraction) and lusitropy (faster relaxation). Protein Gs
stimulates Rho GTPases and mitogen-activated protein kinases (MAPK). Trimer Gi-G

Parasympathetic and sympathetic ( α

inhibits
ACase and stimulates PLC, NOS, and PI3K pathways, thus targeting PKC (cell conditioning),
PKG (antiproliferative and negative inotropy), and PKB (anti-apoptotic), respectively. Trimer Gq-
G

βγ

also activates the PLC, NOS, and PI3K pathways. PKC stimulates and PKA inhibits the
activity of adenylate cyclases (positive and negative feedback loops). Reduced arginine can form
superoxide and reactive nitric oxide species (RNOS). Superoxide rapidly converts NO to RNOS
(Source: [ 650 ]).

βγ

Parasympathetic Sympathetic ( α )

Neurotransmitter Acetylcholine Noradrenaline

GPCR M 2 α 1 α 2

G Protein Gi/G βγ Gi/G βγ Gs

Gq/G βγ Gi/G βγ

First effectors ACase ( − ) ACase ( − ) ACase ( − )

PLC PLC PLC

NO/GCase NO/GCase NO/GCase

PI3K PI3K PI3K

Second messengers cAMP

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

RNOS/cGMP RNOS/cGMP RNOS/cGMP

PDK1 PDK1 PDK1

Protein kinases PKB/PKC/PKG PKB/PKC/PKG PKA/PKB/PKC/PKG

distributed throughout the body. Efferent nerves connect to nodal tissue and
myocardium, controlling primarily the heart frequency and contractility. Efferent
nerves to the smooth muscles in coronary vessel walls control arterial tone, arteriolar
resistance, and blood volume in the large veins.
Normally, parasympathetic innervation is the dominant neural influence on
the heart. However, the adrenergic system, with its various specific G-protein-
coupled receptors and their corresponding cell signaling cascades, yields the major
regulatory system, whereas the parasympathetic system plays a minor role in
responses to environmental stimuli.
Galanin (Gal), a neuropeptide that is cleaved from preprogalanin, inhibits
neurotransmitters. Galanin increases mean arterial blood pressure and heart rate,
inhibiting cholinergic activity in the heart in cooperation with neuropeptide Y
(NPY). Activated Gal1 and NPY-Y2 receptors of parasympathetic terminals of vagal
neurons in the heart reduce acetylcholine release, especially during prolonged atten-
uation of parasympathetic slowing following activation of the cardiac sympathetic
nerve [ 651 ].