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53 Cards in this Set
- Front
- Back
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What type of a neurotransmitter is norepinephrine?
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Catecholamine
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Precursor for NE synthesis:
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Tyrosine
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Where does NE synthesis occur?
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In the brain
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Where are Noradrenergic neurons located?
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Brain - Oblongata, pons, medulla, midbrain.
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What system is activated by NE?
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The reticular activating system.
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What is regulated by NE?
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Wakefulness
BP Breathing |
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What is the pathway for going from Tyrosine to Norepinephrine?
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Tyrosine to L-Dopa
L-Dopa to Dopamine Dopamine to Norepinephrine |
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What are the 3 enzymes for the tyrosine -> NE pathway?
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1. Tyrosine Hydroxylase
2. L-DOPA decarboxylase 3. Dopamine beta hydroxylase |
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Where is Dopamine b-hydroxylse found?
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In vesicles - coreleased along with the NE that it makes.
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Where is Dopa Decarboxylase located?
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In the cytoplasm of the presynaptic neuron; also in astrocytes and serotonergic neurons.
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Which step in NE synthesis is rate-limiting?
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The first step - Tyr Hydroxylase
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Why is Tyrosine Hydroxylase the rate-limiting step?
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Because it is regulated by availability of THB (tetrahydrobiopterin).
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How is Tyrosine Hydroxylase regulated?
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-Phosphorylation at 4 sites
-Feedback inhibition by NE -Long-term by transcription |
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How does NE cause feedback inhibition?
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NE prevents THB from binding to the enzyme TB.
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How can NE prevent THB from binding TH if NE hasn't even been made yet (in vesicle)?
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If the vesicle is overfilled NE will spill out into cytoplasm where TH is.
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What regulates the phosphorylation of TH?
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-Calcium
-cAMP |
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How does phosphorylation affect TH activity?
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It increases it.
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What are the transporters for taking up Dopamine into vesicles for NE synthesis?
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VMATS - vesicle monoamine transporters.
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Where is VMAT2?
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In the brain
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3 mechanisms of NE release:
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-Calcium dependent (normal)
-Reversal of PMTs -Dendridic non-Ca dependent |
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What is primarily responsible for regulating release of NE from presynaptic vesicles?
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Autoreceptors
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What are the autoreceptors for NE, and how do they act?
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-Alpha2 - inhibits release
-Beta - increases release |
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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 |
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What is one mechanism by which ALL Neurotransmitters can be inactivated?
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Diffusion - just float away from the synaptic cleft.
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What is the most important mechanism for inactivation of NE?
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Reuptake by the presynaptic neuron - NOT by astrocytes.
NAT is the transporter |
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What is NAT, how does it work, where is it
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Hgh affinity carrier protein for selective neuron reuptake of NE
-Sodium symporter -May be inhibited by competition |
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What is the fate of NE after reuptake by the presynaptic neuron?
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-Repackage into vesicles
-Degradation by enzymes |
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What are the 2 enzymes that cause inactivation of NE?
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-MAO - monoamine oxidase
-COMT - catechol-o-methyl transferase |
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Where is MAO found?
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On the outer mitochondrial membrane
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What are 2 isoforms of MAO? Where is each located?
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MAOa - in liver
MAOb - in brain |
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What does MAO do to NE?
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Deaminates it
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What is the mechanism of Catechol-O-methyl transferase?
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Transfers a methyl group from SAM to norepinephrine.
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What is MHPG?
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-The primary metabolite of NE; -Product of norepinephrine being acted on by both MAO and COMT.
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Where is COMT located?
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Extracellular - so it would have to act on NE first, then reuptake, then acted on by intracellular MAO.
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What are the receptors for NE called?
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Adrenergic
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How many receptors are there for NE? What type of receptor are they?
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9 - metabotropic
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What else can NE receptors bind?
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Epinephrine
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Main difference between alpha and beta adrenergic receptors:
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-Alpha bind NE better than epi
-Beta bind Epi better than NE |
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Where are Alpha1 receptors?
Where are Alpha2 receptors? |
Alpha1 = postsynaptic
Alpha2 = presynaptic |
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What is the function of Alpha1 receptors?
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Excitatory in the peripheral nervous system - binding to NE increases calcium in the postsynaptic effector (muscle).
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What is the function of Alpha2 receptors?
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Feedback Inhibition of norepi release from presynaptic neurons.
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How do alpha2 receptors work?
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By decreasing adenylyl cyclase
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How do Beta receptors work?
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All beta receptors increase adenylyl cyclase activity
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What physiology is regulated by NE alpha receptors?
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-Arousal/stimulation
-Information gating/focus |
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What physiology is regulated by NE beta receptors?
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-Autonomic outflow
-BP regulation |
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Activation of NE alpha receptors results in:
Inhibition results in: |
Activation = arousal
Inhibition = sleep |
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3 drugs that inhibit the inactivation of NE:
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-Amphetamine
-Methamphetamine and Ritalin -TCA tricycl. antidepressants |
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So what is the overall affect of these drugs?
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STIMULATION (arousal/wakefulness)
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How does Ritalin help ADHD?
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It increases focus and gating of information.
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How does Amphetamine work?
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It makes the NE reuptake carrier reverse so more NE is put into the synaptic cleft.
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How do TCAs work?
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By inhibiting NE reuptake - but that's not their main effect; rather in downregulating receptors and TURNING DOWN the postsynaptic response to NE.
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Both NE alpha receptor AGONISTS and beta receptor BLOCKERS are useful for what?
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Reducing sympathetic outflow - ANTIhypertension
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What is the effect of an alpha ANTAGONIST?
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Blockage of vasoconstriction at the blood vessel.
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