BASIC AGONIST/LIGAND-RECEPTOR PAIRS OF THE CARDIOVASCULAR SYSTEM
Receptor
Tissue/Effector
Response
MECHANISM
Sympathetic nervous system (adrenergic: norepinephrine, epinephrine)
Norepinephrine or
Epinephrine: a1
Vascular smooth muscle
Vasoconstriction
IP3 pathway
Opening of L-type calcium channels
Both will increase intracellular
calcium concentration inside the
vascular smooth muscle
Norepinephrine or
Epinephrine:: a2
Vascular smooth muscle
Norepinephrine or
Epinephrine: b1
SA node, AV node
Vasoconstriction
Increase heart rate
Increase conduction velocity of action
potential
Not in the test
­adenyl cyclase/cAMP/PKA activity =>
­ open probability of HCN channels
and L-type calcium channels
Increase MVO2
Norepinephrine or
Epinephrine: b1
Cardiomyocytes: Ventricular
muscle; atrial muscle
Increase myocardial contractility
(inotropic effect)
Increase myocardial relaxation
(lusitropic effect)
Increase MVO2
­adenyl cyclase/cAMP/PKA activity =>
For the inotropic effect:
­ open probability of L-type calcium
channels
­ open probability of ryanodine
receptor = ­ calcium release from SR
For the lusitropic effect:
Phosphorylation of phospholamban
Phosphorylation of SR calcium ATPase
which increases its activity
Phosphorylation of Troponin I which
destabilizes the binding between
Troponin C and calcium
Norepinephrine or
Epinephrine: b2
Vascular smooth muscle
(Coronary and skeletal
arterioles)
Vasodilation
Mechanism for b2 will not be in the
test:
­adenyl cyclase/cAMP/PKA activity=>
Phosphorylation of MLCK => ¯MLCK
activity
Parasympathetic nervous system (muscarinic: acetylcholine)
Acetylcholine: M2
SA node, AV node
Acetylcholine: M3
Vascular smooth muscle
Decrease heart rate
¯adenyl cyclase/cAMP/PKA activity =>
Decrease conduction velocity of action
¯ open probability of HCN channels
potential
and L-type calcium channels
Opening of GIRK channels
Vasoconstriction
(seen with endothelial dysfunction)
PLC/DAG/IP3 pathway
Opening of L-type calcium channels
Above will increase intracellular
calcium concentration inside vascular
smooth muscle
Acetylcholine: M3
Endothelium
Vasodilation (this is the physiologic
response to acetylcholine)
PLC/DAG/IP3 pathway => increased
intracellular calcium=> NO synthesis =>
NO diffuses to vascular smooth
muscle and “binds” to guanylate
cyclase => increased open probability
of calcium activated potassium
channels => hyperpolarization of
vascular smooth muscle. In addition,
an increase in intracellular calcium in
endothelial cells will increase the
open probability of calcium-activated
potassium channels =>
hyperpolarization => negative charge
transmitted to vascular smooth
muscle via gap junctions.