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 a2 Adrenergic Receptors: Inhibition of adenyl cyclase through G 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 <Clon he 异丙肾上腺素 a R(AC PLC 冷B DG 工 cAMP ⊙ 个cAMP 个Ca PKA)O 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(B1); vasodilation of blood vessels in muscle(β2) Hypoglycemia -response is mainly metabolic ( glycogenolysis 阝2anda1, gluconeogenesisβ2andc12, lipolysisβesp.β3, a2), but B2 vasodilation in muscle increases glucose delivery Hypothermia- piloerection( M), peripheral vasocontraction (Ol), 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
Summary: Adrenoceptors a receptors a, receptors: vasoconstriction: increased peripheral resistance, BP r, contraction of radial muscle of iris: mydriasis a2 receptors: CNS, presynaptic membranes of adrenergic nerves: vasodilatation inhibition of ne release inhibition of insulin release
receptors • 1 receptors: vasoconstriction: increased peripheral resistance, BP↑; contraction of radial muscle of iris: mydriasis • 2 receptors: CNS, presynaptic membranes of adrenergic nerves: vasodilatation, inhibition of NE release; inhibition of insulin release Summary: Adrenoceptors 11