Norepinephrine and Epinephrine Metabolism 9o-t-9- Mo MHPG(3-甲氧4羟苯乙二醇): was used as CH3 an index of cns ne turnover Norepinephrine DOPGAL Epinephrine but generated mostly from aldehyde aldehyde reductase dehydrogenase COMT raphe MMA香草扁桃酸) sometimes used as an index of ne turnover Normetanephrine DOPEG DOMA Metanephrine Sulfate conjugates COMT COMT also prevalent CH,o OH H Elimination by kidneys MOPEG or MHPG VMA Urine MIPG-SO aldehyde reductase NMN-SO MN-SO CHao MAO MAO Relative amounts excreted MOPGAL
Norepinephrine and Epinephrine Metabolism MHPG (3-甲氧4-羟苯乙二醇): was used as an index of CNS NE turnover but generated mostly from periphery VMA(香草扁桃酸): sometimes used as an index of NE turnover Sulfate conjugates also prevalent or MHPG 6
Adrenergic Receptor Subtypes& G-Protein Coupled Mechanisms a Adrenergic Receptors Phospholipase C activation, IP3 increase through G Mechanism mobilize and increase intracellular free calcium Effects: primarily smooth muscle contraction a Adrenergic Receptors nhibition of adenyl cyclase through Gi proteins Mechanism decrease intracellular cAMP levels Effects: decrease protein phosphorylation, decrease cellular function
1 Adrenergic Receptors: Phospholipase C activation, IP3 increase through Gq Mechanism: mobilize and increase intracellular free calcium Effects: primarily smooth muscle contraction 2 Adrenergic Receptors: Inhibition of adenyl cyclase through Gi proteins Mechanism: decrease intracellular cAMP levels Effects: decrease protein phosphorylation, decrease cellular function Adrenergic Receptor Subtypes & G-Protein Coupled Mechanisms 7
Adrenergic Receptor Subtypes& G-Protein Coupled Mechanisms B Adrenergic Receptors Activation of adenyl cyclase through Gs proteins Mechanism increase intracellular camp levels Effects: phosphorylation of intracellular proteins, smooth muscle relaxation cardiac muscle contraction
β Adrenergic Receptors: Activation of adenyl cyclase through Gs proteins Mechanism: increase intracellular cAMP levels Effects: phosphorylation of intracellular proteins, smooth muscle relaxation, cardiac muscle contraction Adrenergic Receptor Subtypes & G-Protein Coupled Mechanisms 8
Receptor 可乐定 Subtypes 去氧肾上腺素 CLor> 异丙肾上腺素 G IRAC PLC DG 工 acAMP |↑cAMP ↑Ca ∠④ KA P 9
q 去氧肾上腺素 异丙肾上腺素 可乐定 9
Four Major activators of the adrenergic system Hypoxia-response is mainly cardiovascular: increase in heart rate contractility(1); vasodilation of blood vessels in muscle(β2) Hypoglycemia -response is mainly metabolic glycogenolysis 阝2anda, gluconeogenesisβ2anda12, ypolysisβesp.阝3, a,), but B2 vasodilation in muscle increases glucose delivery Hypothermia-piloerection(M), peripheral vasocontraction (a), thermogenesis(B Hypotension - baroreceptor reflex 10
• Hypoxia - response is mainly cardiovascular: increase in heart rate & contractility (b1 ); vasodilation of blood vessels in muscle (b2 ). • Hypoglycemia - response is mainly metabolic (glycogenolysis b2 and 1 , gluconeogenesis b2 and 1,2, lypolysis b esp. b3 , 2 ), but b2 vasodilation in muscle increases glucose delivery. • Hypothermia - piloerection (M), peripheral vasocontraction (1 ), thermogenesis (b) • Hypotension – baroreceptor reflex Four Major Activators of the Adrenergic System 10