Transcript Receptors

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