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Published byHector Cummings Modified over 9 years ago
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Receptors Lesson 8
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Ligands & Receptors n Ligand l neurotransmitters l drugs n Receptor proteins l ligand binds to multiple receptors l receptor subtypes l specificity ~
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Ligand-Receptors Binding n Binding site l specific point of ligand & receptor n Affinity l attraction l physical & electrical fit n NT or drug binds to receptor l or activity of neuron l excite or inhibit n Drugs mimic or block NT message ~
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Lock & Key Model n Receptor changes shape n Excitation or Inhibition? l Determined by nature of receptor l receptor subtypes n NOT NT ~ n NT binds to receptor l NT = key l Receptor = lock
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Receptor A NT n ligand binds to receptor l activation: EPSP or IPSP ~
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Receptor B Receptor A n Same NT can bind to different -R l different part of NT ~ NT
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Receptor B Receptor A n Same NT can bind to different -R l different part of NT ~ NT
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Receptor B Receptor A NT Specificity of drugs Drug A Drug B
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Structure-activity relationship n NT fits receptor site u key & lock n Change structure of drug... l change its affinity u increase or decrease l may bind to different receptor n Behavior mediated by synaptic activity l most drugs act at synapse ~
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RECEPTOR DRUG n ligand binding n drug fx ~ Amphetamine NH 2
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RECEPTOR DRUG n ligand binding n drug fx ~ Amphetamine NH 2
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RECEPTOR DRUG n Stronger binding n greater fx ~ NH 2 MDA
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RECEPTOR DRUG n Stronger binding n greater fx ~ MDMA NH
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Drug Interaction Terms n Agonist (AG) mimics or NT effects n Antagonist (ANT) blocks or NT effects ~
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Drug Interaction Terms n Direct agonist l activates receptor n direct antagonist l also binds to postsynaptic receptor l does not activate n Indirect (agonist/antagonist) l affects other parts of synaptic transmission model ~
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Drug Interaction Terms n Competitive antagonist l competes for same receptor site l < affinity of NT n Noncompetitive l same binding site, >> affinity than NT l or different binding site on receptor ~
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Drug Interaction Terms n Allosteric interactions l At different site, same receptor l noncompetitive antagonism l Potentiation (agonistic) n Partial agonist l activates -R, but weaker than NT n Inverse Agonist l activates receptor l opposite effect of NT ~
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RECEPTOR NT Antagonists NT ANT
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RECEPTOR NT Antagonists NT ANT
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Receptor Types n Ionotropic receptors l NT directly controls channel l fast & transient action l Rapid desensitization u Tachyphylaxis n Metabotropic receptors l G protein-coupled receptors l requires energy: GTP l neuromodulation ~
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Metabotropic receptors n G protein-gated Ion Channels l Receptor indirectly controls channel l relatively fast n 2d messenger systems l Effects relatively slow l long-lasting l Signal amplification ~
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G protein-gated Ion Channels R G GDP
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G protein-gated Ion Channels R G GTP Pore
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2d Messenger Effects n Modulate phosphorylation l activation of processes l Protein Kinases l Protein Phosphatases n Modulate gene expression l transcriptional factors l DNA RNA Proteins l e.g., -R up- or down-regulation ~
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n External signal l NT = 1st messenger n Membrane-associated components l Receptor l Transducer l Primary effector n Intracellular l 2d messenger l Secondary effector ~ 2d Messenger Systems
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G protein: Protein Phosphorylation Receptor trans- ducer primary effector external signal: nt 2d messenger secondary effector Receptor trans- ducer primary effector external signal: nt 2d messenger secondary effector GSGS norepinephrine cAMP protein kinase A adrenergic -R adenylyl cyclase
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2d Messenger Systems n External signal n Receptor n Transducer n Primary effector n 2d messenger n Secondary effector ~ n Norepinephrine n Beta-adrenergic-R n G s –protein n Adenylyl cyclase n cAMP n Protein Kinase A
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G protein: Protein Phosphorylation R G GTP ACAC GDP * PKA
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G protein: Protein Phosphorylation R ACAC PKA G GTP ATP cAMP P Pore
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