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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
Receptor changes shape Excitation or Inhibition?
Determined by nature of receptor receptor subtypes
NOT NT ~
NT binds to receptor NT = key Receptor = lock
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 ~
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 ~
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 ~
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 ~
External signal NT = 1st messenger
Membrane-associated components Receptor Transducer Primary effector
Intracellular 2d messenger Secondary effector ~
2d Messenger Systems
G protein: Protein Phosphorylation
Receptor
trans-ducer
primaryeffector
external signal: nt
2d messenger
secondary effector
Receptor
trans-ducer
primaryeffector
external signal: nt
2d messenger
secondary effector
GS
norepinephrine
cAMP
protein kinase A
adrenergic -R
adenylylcyclase
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
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