Lecture 11 Adrenaline Rush Through cAMP

Lecture 11 Adrenaline Rush Through cAMP - LR (active)...

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10/11/11 1 An Adrenalin Rush Through cAMP
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10/11/11 2
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10/11/11 3 Earl Sutherland, 1971 1) Identifed cAMP as generated in liver cells aFter exposure to adrenaline 2) Demonstrated cAMP added to liver cells caused same response as adrenaline.
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10/11/11 4
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10/11/11 5 caffeine X
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10/11/11 6 NEM poisons AC enzyme by covalent modifcation. Forskolin stimulates enzyme. Sutherland’s Model
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10/11/11 7 Reconstitution of Adrenaline response demonstrates the necessity of adrenaline receptor. Red blood cells: have AR and AC Adrenal cortex cells: have no AR but have AC Response (cAMP levels) no AR low AR med AR high AR -Adrenaline +Adrenaline Receptor Activation R (inactive) -----> R (active) ----->
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Unformatted text preview: LR (active) Monomer Dimer Dimer 10/11/11 8 Activation (response) Ligand binding 10/11/11 9 10/11/11 10 Sutherlands Model Martin Rodbell, 1967 10/11/11 11 experimental genetics approach to isolate a cyc-mutant used S49 lymphoma cells selection criteria: 1. growth in presence of adrenaline 2. maintain receptors that bind adrenaline result : obtained cells that bound adrenaline but with no response. BUT, some of these still had a forskolin response! HOW??? Many of these cells had defective AC enzymes. Alfred Gilman 10/11/11 12 10/11/11 13 10/11/11 14 adrenaline Gs G AR dimer Adenylate Cyclase 10/11/11 15...
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Lecture 11 Adrenaline Rush Through cAMP - LR (active)...

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