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G q. a 1. [Ca] intracellu lar á. a. a 2. [cAMP] â. G i. G s. b 1. [cAMP] á. b. [cAMP] á. b 2. G s. [cAMP] á. b 3. Az adrenerg ic receptor s (Michelotti et al, Pharmacol.Ther. 88, 281-309, 2000).

avram-caldwell
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  1. Gq a1 [Ca]intracellulará a a2 [cAMP] â Gi Gs b1 [cAMP] á b [cAMP] á b2 Gs [cAMP] á b3

  2. Az adrenergic receptors(Michelotti et al, Pharmacol.Ther. 88, 281-309, 2000)

  3. Physiological actions of adrenergic receptor stimulation(Michelotti et al, Pharmacol.Ther. 88, 281-309, 2000)

  4. Subtypes of ß-adrenergic receptors

  5. Noradrenergic innervation Hormon action relaxation positive ino- and chronotrop relaxation Glycogen breakdown Vasodilation lipolysis relaxation ß3 lipolysis

  6. ß1 RECEPTORS IN THE HEART

  7. 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 åfrom 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

  8. Late action Phospholambane èinhibits SR Ca2+-ATP-ase (only in the heart) cAMP-dependent protein kinaseèphosphorylation of phospholambane(inhibition)èSR Ca2+-ATP-ase is activated Increased heart rate In the therapy: ß1-selective antagonists Arrhytmia Anginaèdecrease in the frequency of contractions

  9. Noradrenergic innervation Hormon action relaxation positive ino- and chronotrop relaxation Glycogen breakdown Vasodilation lipolysis relaxation ß3 lipolysis

  10. ADIPOSE TISSUE ß1AND ß3RECEPTORS cAMP á cAMP-dependent protein kinase Glycogen synthase Hormon sensitive lipase Glycogen phosphorylase kinase LIPOLYSIS GLYCOGENOLYSIS Inhibiton of GLYCOGEN SYNTHESIS

  11. ADIPOSE TISSUEα RECEPTORS a2 - receptor a1 - receptor Ca-calmodulin cAMP â Inhibition of LIPOLYSIS GLYCOGENOLYSIS Inhibition of GLYCOGEN SYNTHESIS

  12. Noradrenergic innervation Hormon action relaxation positive ino- and chronotrop relaxation Glycogen breakdown Vasodilation lipolysis relaxation ß3 lipolysis

  13. 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 α1 _Ca-CAM Myosin light chain (20000 Da) phosphorylation (19Ser-OH) Actin - myosin Contraction

  14. 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 Increasedglycogenolysis Smooth muscle relaxation Bronchi Blood vessels intestine

  15. 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 α1 _Ca-CAM Myosin light chain (20000 Da) phosphorylation (19Ser-OH) Actin - myosin Contraction

  16. Blood vessels a1 Adrenaline Ergot alkaloids Adrenaline b2 a-receptor blocker

  17. The physiological effects of a1-adrenerg receptors Myocardium *Positiv Inotrop effect – less important than β receptors *cardiac insufficiency - β receptor desenzitization and down-regulation – effect of a1becomes 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)

  18. in aging increased a1 receptor expression + increase in plasma [catecholamine] +β receptor desenzitization in the miocardium →HYPERTENSION

  19. 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 Increasedglycogenolysis Smooth muscle relaxation Bronchi Blood vessels intestine

  20. a2 receptors on the cholinergic axon terminals in the GI tract Muszkarin ß kontrakció relaxáció NA ACh a2

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