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First messenger - Neurotransmitters & drugs
Receptor proteins - ligand binds to?
Ligand binds to multiple receptors
What is a Binding site?
Specific point of ligand & receptor
- Physical & electrical fit
= neurotransmitters made by the brain
- Yellow = brain cell
- Endocrine process
- Endocrine system
- Paracrine proces- cell makes signals to surrounding cells
- Autocrine process � cell makes signals to itself
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
passing of the message; message remains exactly the same
The overflow of information during cell signaling
- Hydrophilic signal � prinmary messenger � Hydrophobic signal
- Plasma membrane Intracelllular receptor
- Lined to protein kinase
- Linked to g protein Signal proteins
- a)Cyclic AMP
- b)IP3, DAG, Ca2+ Second messenger
Chemical Signaling Mechanisms
- Medium range intercellular signaling
- Hormones via blood
- Via air ~
Signaling Pathways:Cell impermeable requires?
Requires receptor in membranes
Signaling Pathways: Cell permeable
- Lipid soluble
- Steroid hormones
Signaling Pathways: cell associated signaling molecules
- Signal transduction pathway can amplify the cellular response on an external signal
Hydrophobic will pass through membrane and
do not need receptor
Hydrophylic will not pass
For hydrophobic ligand
also need receptor for proteins
Receptor Types: Channel linked receptors
Receptor Types: Enzyme linked receptors
- Protein kinase mostly
- Neurotrophin � R
Receptor Types:G protein �
- coupled receptors
Receptor Types: Intracellular receptors
Activated by cell � permanent signals
G Protein coupled receptors
Metabotropic receptors Requires
Metabotropic receptors: Receptor indirectly controls channel
- G protein � gated ion channel
- 2d messenger systems
Metabotropic receptors: Neuromodulation
- Slower action
- Change in sensitivity of neuron
G protein-gated Ion Channels: NT binds to
G protein-gated Ion Channels: NT binds to receptor protein which activates
2d Messenger Systems NT is ?
First Messenger --> Ligand Membrane --> associated componentsReceptorTransductionPrimary effector
G protein binds to channel which does what?
- opens or closes
- relatively fast
- 2d messenger
- Secondary effector
- Slower & enduring changes
- Multiple effectors
- 1 NE � 1000s cAMP
- 1000s cAMP � 10,000s phosphates
2d Messenger Systems: Effects
- Control channel
- Alter properties of receptors
- regulation of gene expression ~
- Calcium (Ca2+)
- Target: calmodulin
protein kinases & phosphatases
Cyclic nucleotides cAMP & cGMP activates?
- (Activates Kinases)
- Target: protein kinases ~
- Increased concentration cyclic AMP activates kinases
The structure and metabolism of cAMP. cAMP is generated by
The enzyme of cAMP is
enzyme adenylyl cyclase
2d messenger: Diacylglycerol
DAG --> protein kinase C (membranes)
2d Messengers: Membrane Lipids
- Precursor PIP2
- Phoshatidylinositol bisphosphate Cleaved by phosphylipase C
cAMP It is inactivated by hydrolysis of AMP, a reaction catalyzed by
2d MEssenger: Inositol triphosphate
- IP3 --> Ca2+ (ER) --> Frees Ca2+ from inside to outside
- Diacylglycerol & Inositol triphosphate
- Activates DAG ---> Protein kinase C and calcium
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.
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.
2d Messenger Targets: Enzymes
2d Messenger Targets:: Protein Kinase
- Activated by: Ca2+, CAMP, DAG, etc.
- Increases phosphorylation
2d Messenger Targets: Protein Phosphatases
- Decreases phosphoryation
- Activated by Ca2+/Calmodulin
The release of calcium ion and signal processes.
Calcium plays an essential role in regulating cellular function
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.)