1. dia

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(No Transcript)
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Gq
a1
Caintracellular á
a
a2
cAMP â
Gi
Gs
b1
cAMP á
b
cAMP á
b2
Gs
cAMP á
b3
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Az adrenergic receptors (Michelotti et al,
Pharmacol.Ther. 88, 281-309, 2000)
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Physiological actions of adrenergic receptor
stimulation (Michelotti et al, Pharmacol.Ther.
88, 281-309, 2000)
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Subtypes of ß-adrenergic receptors
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Noradrenergic innervation
Hormon action
positive ino- and chronotrop
relaxation
relaxation
Glycogen breakdown Vasodilation
lipolysis
relaxation
ß3
lipolysis
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ß1 RECEPTORS IN THE HEART
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ß1 RECEPTORS IN THE HEART

• 1. Immediate action
• cAMP-dependent protein kinase
• â
• Phosphorylation of plasma membrane Ca2-channels
• â
• Ca2 entry à Ca2 induced Ca2 release
• â å from Sarcoplasmic reticulum
• Rise in intracellular Ca2
• Þ
• Increased force of contraction -Positive
  inotropic effect
• 2. Late action
• Activation of sarcoplasmic reticulum Ca2-ATP-ase
• Þ
• Ca2 sequestration

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• Late action
• Phospholambane è inhibits SR
  Ca2-ATP-ase
• (only in the heart)
• cAMP-dependent protein kinase è phosphorylation
  of phospholambane (inhibition) è SR
  Ca2-ATP-ase is activated
• Increased heart rate
• In the therapy ß1-selective antagonists
• Arrhytmia
• Angina è decrease in the frequency of
  contractions

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Noradrenergic innervation
Hormon action
positive ino- and chronotrop
relaxation
relaxation
Glycogen breakdown Vasodilation
lipolysis
relaxation
ß3
lipolysis
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ADIPOSE TISSUE ß1 AND ß3 RECEPTORS
cAMP á
cAMP-dependent protein kinase
Hormon sensitive lipase
Glycogen phosphorylase kinase
Glycogen synthase
LIPOLYSIS
GLYCOGENOLYSIS
Inhibiton of GLYCOGEN SYNTHESIS
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ADIPOSE TISSUE a RECEPTORS
a2 - receptor
a1 - receptor
Ca-calmodulin
cAMP â
Inhibition of LIPOLYSIS
GLYCOGENOLYSIS
Inhibition of GLYCOGEN SYNTHESIS
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Noradrenergic innervation
Hormon action
positive ino- and chronotrop
relaxation
relaxation
Glycogen breakdown Vasodilation
lipolysis
relaxation
ß3
lipolysis
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Bronchi ß2 Intestinal smooth muscle ß1 Uterus
ß2 (Blood vessels ß2)
Smooth muscle
cAMP é
cAMP-depentent protein kinase
Dephosphorylated Myosin light chain
kinase (active)
Phosphorylated Myosin light chain
kinase (inactive)
Catalytic subunit
Relaxation
Active myosin light chain kinase
a1 _Ca-CAM
Myosin light chain (20000 Da) phosphorylation
(19Ser-OH)
Actin - myosin
Contraction
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ACTIONS MEDIATED THROUGH
a1 Increased glycogenolysis Smooth muscle
contraction In blood vessels
a2 Intestinal smooth muscle relaxation Inhibition
of lipolysis, platelet aggregation
ß1 Stimulation of lipolysis Increased heart rate
force
ß2 Increased glyconeogenesis Increased
glycogenolysis Smooth muscle relaxation Bronchi
Blood vessels intestine
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Bronchi ß2 Intestinal smooth muscle ß1 Uterus
ß2 (Blood vessels ß2)
Smooth muscle
cAMP é
cAMP-depentent protein kinase
Dephosphorylated Myosin light chain
kinase (active)
Phosphorylated Myosin light chain
kinase (inactive)
Catalytic subunit
Relaxation
Active myosin light chain kinase
a1 _Ca-CAM
Myosin light chain (20000 Da) phosphorylation
(19Ser-OH)
Actin - myosin
Contraction
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Blood vessels
a1
Adrenaline
Ergot alkaloids
Adrenaline
b2
a-receptor blocker
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The physiological effects of a1-adrenerg receptors

• Myocardium
• Positiv Inotrop effect less important
  than ß receptors
• cardiac insufficiency - ß receptor
  desenzitization and down-regulation effect of
  a1 becomes significant
• long-term a1 stimulation miocardial
  hypertrophy
• Blood vessels
• vazokonstruction in the non essential
  vessels (splanchnic) blood supply to the
  essential organs receives priority (brain, heart)
  

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in aging increased a1 receptor expression
increase in plasma
catecholamine ß receptor desenzitization
in the miocardium ?HYPERTENSION
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ACTIONS MEDIATED THROUGH
a1 Increased glycogenolysis Smooth muscle
contraction In blood vessels
a2 Intestinal smooth muscle relaxation Inhibition
of lipolysis, platelet aggregation
ß1 Stimulation of lipolysis Increased heart rate
force
ß2 Increased glyconeogenesis Increased
glycogenolysis Smooth muscle relaxation Bronchi
Blood vessels intestine
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a2 receptors on the cholinergic axon terminals in
the GI tract
Muszkarin
ß
kontrakció
relaxáció
NA
ACh
a2