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Ligand
First messenger - Neurotransmitters & drugs
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Receptor proteins - ligand binds to?
Ligand binds to multiple receptors
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What is a Binding site?
Specific point of ligand & receptor
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Affinity
- Attraction
- Physical & electrical fit
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Ligands
= neurotransmitters made by the brain
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Picture
- Yellow = brain cell
- Endocrine process
- Endocrine system
- Paracrine proces- cell makes signals to surrounding cells
- Autocrine process � cell makes signals to itself
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Cell contains receptors, if the ligand fits, a cascade of chemical changes will occur to tell the DNA to make
specific proteins, enzymes, or hormones
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Signal transduction
passing of the message; message remains exactly the same
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The overflow of information during cell signaling
- Hydrophilic signal � prinmary messenger � Hydrophobic signal
- Plasma membrane Intracelllular receptor
- Receptor:
- Lined to protein kinase
- Linked to g protein Signal proteins
- a)Cyclic AMP
- b)IP3, DAG, Ca2+ Second messenger
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Chemical Signaling Mechanisms
- Synaptic
- Paracrine
- Medium range intercellular signaling
- Endocrine
- Hormones via blood
- Pheromones
- Via air ~
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Signaling Pathways:Cell impermeable requires?
Requires receptor in membranes
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Signaling Pathways: Cell permeable
- Lipid soluble
- Steroid hormones
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Signaling Pathways: cell associated signaling molecules
- Signal transduction pathway can amplify the cellular response on an external signal
- Ligands
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Hydrophobic will pass through membrane and
do not need receptor
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Hydrophylic will not pass
needs receptors
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For hydrophobic ligand
also need receptor for proteins
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Receptor Types: Channel linked receptors
Isotropic
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Receptor Types: Enzyme linked receptors
- Protein kinase mostly
- Neurotrophin � R
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Receptor Types:G protein �
- coupled receptors
- Metabotropic
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Receptor Types: Intracellular receptors
Activated by cell � permanent signals
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Metabotropic receptors
G Protein coupled receptors
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Metabotropic receptors Requires
GTP
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Metabotropic receptors: Receptor indirectly controls channel
- G protein � gated ion channel
- 2d messenger systems
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Metabotropic receptors: Neuromodulation
- Slower action
- Change in sensitivity of neuron
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G protein-gated Ion Channels: NT binds to
receptor protein
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G protein-gated Ion Channels: NT binds to receptor protein which activates
G protein
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2d Messenger Systems NT is ?
First Messenger --> Ligand Membrane --> associated componentsReceptorTransductionPrimary effector
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G protein binds to channel which does what?
- opens or closes
- relatively fast
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Intracellular
- 2d messenger
- Secondary effector
- Slower & enduring changes
- Multiple effectors
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Signal amplification
- 1 NE � 1000s cAMP
- 1000s cAMP � 10,000s phosphates
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2d Messenger Systems: Effects
- Control channel
- Alter properties of receptors
- regulation of gene expression ~
- Calcium (Ca2+)
- Target: calmodulin
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Calmodulin activates
protein kinases & phosphatases
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Cyclic nucleotides cAMP & cGMP activates?
- (Activates Kinases)
- Target: protein kinases ~
- Increased concentration cyclic AMP activates kinases
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The structure and metabolism of cAMP. cAMP is generated by
ATP.
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The enzyme of cAMP is
enzyme adenylyl cyclase
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2d messenger: Diacylglycerol
DAG --> protein kinase C (membranes)
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2d Messengers: Membrane Lipids
- Precursor PIP2
- Phoshatidylinositol bisphosphate Cleaved by phosphylipase C
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cAMP It is inactivated by hydrolysis of AMP, a reaction catalyzed by
phosphodiesterase
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2d MEssenger: Inositol triphosphate
- IP3 --> Ca2+ (ER) --> Frees Ca2+ from inside to outside
- Diacylglycerol & Inositol triphosphate
- Activates DAG ---> Protein kinase C and calcium
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IP3 is made from PIP2 as uncommon phospholipid membrane where the enzyme phoapholipase C is acivated. Phosphylipase C cleaves PIP2 into
2 molecules of IP3 and DAG.
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Roles of IP3 and DAG as second messengers.
- 1.Ligand binds to receptor
- 2.G-Protein acication
- 3.Gq activates phospholipase C that generates IP3 and DAG
- Inositol triphosphate is water soluble. Diffusing through the cytosol and binding to a calcium channel known as IP3 receptor.
- Then he channel opens releasing calcium to eh cytosol.
- Calcium then elicits the desired physiological response.
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2d Messenger Targets: Enzymes
Modulate phosphorylation
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2d Messenger Targets:: Protein Kinase
- Activated by: Ca2+, CAMP, DAG, etc.
- Increases phosphorylation
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2d Messenger Targets: Protein Phosphatases
- Decreases phosphoryation
- Activated by Ca2+/Calmodulin
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The release of calcium ion and signal processes.
Calcium plays an essential role in regulating cellular function
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The concentration of Ca is very low in the cytosol due to the presence of
- calcium ATPases
- There are several different ways that various stimuli can increase Ca in cytosol (neurotransmitter, fertilization of animal egg, egg activation etc.)
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