Signal Transduction Lecture 14. Ligands & Receptors n Ligand l Neurotransmitters & drugs n Receptor...
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Transcript of Signal Transduction Lecture 14. Ligands & Receptors n Ligand l Neurotransmitters & drugs n Receptor...
Ligands & Receptors Ligand
Neurotransmitters & drugs Receptor proteins
ligand binds to multiple receptors Binding site
specific point of ligand & receptor Affinity
attraction physical & electrical fit~
Receptor Activation Lock & Key Model Structure-activity relationship
Physical & electrical fit Affinity
Activation excitation or inhibition Drugs
Change structure change affinity Agonists activate Antagonists no activation ~
Chemical Signaling Mechanisms
Synaptic Paracrine
Medium range intercellular signaling
Endocrine Hormones via blood
Pheromones Via air ~
Signaling Pathways
Cell impermeant Requires receptors in membranes
Cell permeant Lipid soluble Steroid hormones
Cell-associated signaling molecules e.g., CAMs ~
Receptor Types
Channel-linked receptors Ionotropic
Enzyme-linked receptors Protein kinases mostly Neurotrophin-R
G-protein-coupled receptors Metabotropic
Intracellular receptors Activation by cell-permeant signals ~
Metabotropic receptors G protein-coupled receptors
requires GTP Receptor indirectly controls
channel G protein-gated ion
channels 2d messenger systems
neuromodulation slower action changes in sensitivity of
neuron ~
G protein-gated Ion Channels
NT binds to receptor proteinactivates G protein
G protein binds to channelopens or closesrelatively fast
compared to 2d messenger systems ~
NT = 1st messenger Membrane-associated components
Receptor Transducer Primary effector
Intracellular 2d messenger Secondary effector ~
2d Messenger Systems
2d Messenger Targets
Enzymes Modulate phosphorylation
Protein Kinases activated by: Ca2+ , cAMP, DAG, etc. Increase phosphorylation
Protein Phosphatases Decrease phosphorylation activated by Ca2+/calmodulin ~
2d Messenger Targets: Nuclear Signaling
Modulates protein synthesis Slow: 30-60 min
Transcriptional activator proteins DNA RNA Proteins ~
2d Messenger Systems Slower & enduring changes
Multiple effectors Signal amplification
1 NE 1000s cAMP 1000s cAMP 10,000s phosphates
Effects Control channel Alter properties of receptors regulation of gene expression ~
2d Messengers
Calcium (Ca2+) Target: calmodulin Calmodulin protein kinases &
phosphatases Cyclic nucleotides
cAMP & cGMP Target: protein kinases ~
2d Messengers: Membrane Lipids
Precursor: PIP2 Phosphatidylinositol biphosphate
Cleaved by phospholipase C Diacylglycerol
DAG Protein Kinase C (membrane) Inositol triphosphate
IP3 Ca2+ (endoplasmic reticulum) ~
adrenergic 2d Messenger System
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
adrenergic -R
adenylylcyclase
adrenergic 2d Messenger System
NT: Norepinephrine Membrane-associated components
Receptor: adrenergic Transducer: Gs protein Primary effector: Adenyly cyclase
Intracellular components 2d messenger: cAMP Secondary effector: Protein kinase ~