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53 Cards in this Set

  • Front
  • Back
What type of a neurotransmitter is norepinephrine?
Precursor for NE synthesis:
Where does NE synthesis occur?
In the brain
Where are Noradrenergic neurons located?
Brain - Oblongata, pons, medulla, midbrain.
What system is activated by NE?
The reticular activating system.
What is regulated by NE?
What is the pathway for going from Tyrosine to Norepinephrine?
Tyrosine to L-Dopa
L-Dopa to Dopamine
Dopamine to Norepinephrine
What are the 3 enzymes for the tyrosine -> NE pathway?
1. Tyrosine Hydroxylase
2. L-DOPA decarboxylase
3. Dopamine beta hydroxylase
Where is Dopamine b-hydroxylse found?
In vesicles - coreleased along with the NE that it makes.
Where is Dopa Decarboxylase located?
In the cytoplasm of the presynaptic neuron; also in astrocytes and serotonergic neurons.
Which step in NE synthesis is rate-limiting?
The first step - Tyr Hydroxylase
Why is Tyrosine Hydroxylase the rate-limiting step?
Because it is regulated by availability of THB (tetrahydrobiopterin).
How is Tyrosine Hydroxylase regulated?
-Phosphorylation at 4 sites
-Feedback inhibition by NE
-Long-term by transcription
How does NE cause feedback inhibition?
NE prevents THB from binding to the enzyme TB.
How can NE prevent THB from binding TH if NE hasn't even been made yet (in vesicle)?
If the vesicle is overfilled NE will spill out into cytoplasm where TH is.
What regulates the phosphorylation of TH?
How does phosphorylation affect TH activity?
It increases it.
What are the transporters for taking up Dopamine into vesicles for NE synthesis?
VMATS - vesicle monoamine transporters.
Where is VMAT2?
In the brain
3 mechanisms of NE release:
-Calcium dependent (normal)
-Reversal of PMTs
-Dendridic non-Ca dependent
What is primarily responsible for regulating release of NE from presynaptic vesicles?
What are the autoreceptors for NE, and how do they act?
-Alpha2 - inhibits release

-Beta - increases release
How does Alpha2 receptor inhibit NE release?
How do Beta receptors stimulate NE release?
Alpha: inhibit adenylyl cyclase to decrease Ca sensitivity
Beta: increase adenylyl cyclase activity
What is one mechanism by which ALL Neurotransmitters can be inactivated?
Diffusion - just float away from the synaptic cleft.
What is the most important mechanism for inactivation of NE?
Reuptake by the presynaptic neuron - NOT by astrocytes.

NAT is the transporter
What is NAT, how does it work, where is it
Hgh affinity carrier protein for selective neuron reuptake of NE
-Sodium symporter
-May be inhibited by competition
What is the fate of NE after reuptake by the presynaptic neuron?
-Repackage into vesicles
-Degradation by enzymes
What are the 2 enzymes that cause inactivation of NE?
-MAO - monoamine oxidase
-COMT - catechol-o-methyl transferase
Where is MAO found?
On the outer mitochondrial membrane
What are 2 isoforms of MAO? Where is each located?
MAOa - in liver

MAOb - in brain
What does MAO do to NE?
Deaminates it
What is the mechanism of Catechol-O-methyl transferase?
Transfers a methyl group from SAM to norepinephrine.
What is MHPG?
-The primary metabolite of NE; -Product of norepinephrine being acted on by both MAO and COMT.
Where is COMT located?
Extracellular - so it would have to act on NE first, then reuptake, then acted on by intracellular MAO.
What are the receptors for NE called?
How many receptors are there for NE? What type of receptor are they?
9 - metabotropic
What else can NE receptors bind?
Main difference between alpha and beta adrenergic receptors:
-Alpha bind NE better than epi

-Beta bind Epi better than NE
Where are Alpha1 receptors?
Where are Alpha2 receptors?
Alpha1 = postsynaptic

Alpha2 = presynaptic
What is the function of Alpha1 receptors?
Excitatory in the peripheral nervous system - binding to NE increases calcium in the postsynaptic effector (muscle).
What is the function of Alpha2 receptors?
Feedback Inhibition of norepi release from presynaptic neurons.
How do alpha2 receptors work?
By decreasing adenylyl cyclase
How do Beta receptors work?
All beta receptors increase adenylyl cyclase activity
What physiology is regulated by NE alpha receptors?
-Information gating/focus
What physiology is regulated by NE beta receptors?
-Autonomic outflow
-BP regulation
Activation of NE alpha receptors results in:
Inhibition results in:
Activation = arousal

Inhibition = sleep
3 drugs that inhibit the inactivation of NE:
-Methamphetamine and Ritalin
-TCA tricycl. antidepressants
So what is the overall affect of these drugs?
STIMULATION (arousal/wakefulness)
How does Ritalin help ADHD?
It increases focus and gating of information.
How does Amphetamine work?
It makes the NE reuptake carrier reverse so more NE is put into the synaptic cleft.
How do TCAs work?
By inhibiting NE reuptake - but that's not their main effect; rather in downregulating receptors and TURNING DOWN the postsynaptic response to NE.
Both NE alpha receptor AGONISTS and beta receptor BLOCKERS are useful for what?
Reducing sympathetic outflow - ANTIhypertension
What is the effect of an alpha ANTAGONIST?
Blockage of vasoconstriction at the blood vessel.