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Receptors Lesson 8 Ligands & Receptors Ligand neurotransmitters drugs Receptor proteins ligand binds to multiple receptors receptor subtypes specificity ~ Ligand-Receptors Binding Binding site specific point of ligand & receptor Affinity attraction physical & electrical fit NT or drug binds to receptor or activity of neuron excite or inhibit Drugs mimic or block NT message ~ Lock & Key Model NT binds to receptor NT = key Receptor = lock Receptor changes shape Excitation or Inhibition? Determined by nature of receptor receptor subtypes NOT NT ~ ligand binds to receptor activation: EPSP or IPSP NT Receptor A ~ Same NT can bind to different -R different part of NT ~ NT Receptor A Receptor B Same NT can bind to different -R different part of NT ~ NT Receptor A Receptor B Specificity of drugs Drug A Receptor A NT Drug B Receptor B Structure-activity relationship NT fits receptor site key & lock Change structure of drug... change its affinity increase or decrease may bind to different receptor Behavior mediated by synaptic activity most drugs act at synapse ~ ligand binding drug fx ~ Amphetamine NH2 DRUG RECEPTOR ligand binding drug fx ~ Amphetamine NH2 DRUG RECEPTOR Stronger binding greater fx ~ MDA NH2 DRUG RECEPTOR Stronger binding greater fx ~ MDMA NH DRUG RECEPTOR Drug Interaction Terms Agonist (AG) mimics or NT effects Antagonist (ANT) blocks or NT effects ~ Drug Interaction Terms Direct agonist activates receptor direct antagonist also binds to postsynaptic receptor does not activate Indirect (agonist/antagonist) affects other parts of synaptic transmission model ~ Drug Interaction Terms Competitive antagonist competes for same receptor site < affinity of NT Noncompetitive same binding site, >> affinity than NT or different binding site on receptor ~ Drug Interaction Terms Allosteric interactions At different site, same receptor noncompetitive antagonism Potentiation (agonistic) Partial agonist activates -R, but weaker than NT Inverse Agonist activates receptor opposite effect of NT ~ NT Antagonists NT ANT ANT RECEPTOR NT Antagonists NT RECEPTOR ANT Receptor Types Ionotropic receptors NT directly controls channel fast & transient action Rapid desensitization Tachyphylaxis Metabotropic receptors G protein-coupled receptors requires energy: GTP neuromodulation ~ Metabotropic receptors G protein-gated Ion Channels Receptor indirectly controls channel relatively fast 2d messenger systems Effects relatively slow long-lasting Signal amplification ~ G protein-gated Ion Channels R G GDP G protein-gated Ion Channels R G GTP Pore 2d Messenger Effects Modulate phosphorylation activation of processes Protein Kinases Protein Phosphatases Modulate gene expression transcriptional factors DNA RNA Proteins e.g., -R up- or down-regulation ~ 2d Messenger Systems External signal NT = 1st messenger Membrane-associated components Receptor Transducer Primary effector Intracellular 2d messenger Secondary effector ~ G protein: Protein Phosphorylation external signal: nt norepinephrine Receptor b adrenergic -R transducer primary effector GS adenylyl cyclase 2d messenger cAMP secondary effector protein kinase A 2d Messenger Systems External signal Receptor Transducer Primary effector 2d messenger Secondary effector ~ Norepinephrine Beta-adrenergic-R Gs –protein Adenylyl cyclase cAMP Protein Kinase A G protein: Protein Phosphorylation A C R G GTP * GDP PKA G protein: Protein Phosphorylation A C R G ATP GTP P cAMP PKA Pore