Neurotransmitters

Question 1

How is NE produced?

Answer 1

Transporter picks up tyrosine and brings it to the norepinephrine NT

TOH-tyrosine hydroxinase converts tyrosine to DOPA, DOPA is converted to Dopamine by enzyme DDC (Dopa-decarboxinase?). Dopamine converted to norepinephrine by DBH. It is then taken up in vescicles where it is stored.

Tyrosine is the precursor, several enzymatic actions lead to NE and should know that Dopamine is the precursor to NE and that NE is packaged and released into vescicles

Question 2

How is NE destroyed?

Answer 2

1. NE transporter or the NET carried back into the neuron where it is released and repackaged to be reused.
2. Broken down extracellularly by COMT, when its done doing its action it will take up and break down the NE
3. MAOA, MAOB- enzyme present in the mitochondria within the neuron and within other cells such as glial cells- also breaks down extra NE that didn’t get packaged

Question 3

Where/What are NE receptors

Answer 3

1. NET- is responsible for clearing the NE out of the synapse
2. VMAT-vesicular monamine transporter takes up Ne into synaptic vesicles and stores it for future use
3. Presynaptic alpha 2- which regulated the release of NE from the presynaptic neuron, gives message, transmission is over and its time to pick up extra NE, can close off
4. Post syn. neurons

Question 4

How does the cell know to release NE?

Answer 4

• NE that is packaged into vesicles waits for the electrical impulse which come down the axon and causes it to release into gap.
• How does neuron know not to send out more neurons? Gatekeeper (alpha 2) or when autoreceptor near dendrites is closed ( NE in receptor) it tells neuron to slow down and stop giving electrical impulses.
• How does it know to send more neurons? Alpha 2 receptor on dendrite is open (no NE is in receptor)

Question 5

Where does NE have effect in brain?

Answer 5

• frontal lobe: mood and attention
• limbic: attention, energy level, agitation, emotions
• cerebellum- tremors
• spinal cord- BP
• bladder- urinary retention

Question 6

How is DA produced?

Answer 6

… tyrosine transporter pick up tyrosine and brings it to dopamine NT

• TOH enzyme turn tyrosine into DOPA
• DDC turns DOPA into dopamine
• Gets packaged into vesicles where it is stored until it gets message to release into gap

Question 7

How is DA destroyed?

Answer 7

1. Can be transported back into neuron by DAT, dopamine transporter (designed specifically to pick up DA and puts it back into Nueron where it is repackaged and stroed for future use (then brought to vesicles by VMAT)
2. Through extracellular enzyme (outside of neuron), COMT
3. Destroyed by MAOA and MAOB within (or outside) neuron

Question 8

WHere/What are DA receptors?

Answer 8

1. DAT repackages outside cell and put them back into the cell for future use
2. VMAT2- pick up NT inside cell and brings it to vesicles
3. Post-synaptic receptors
   - Knowing there are 5 receptors helps drug companies make a NT-blocker that is specific to one and cause less side effects. Helps to make drugs specific and study individual receptors
   - there are auto-receptors, Receptors for regulation. In this case, D-2 is auto receptor (on dendrites), when it is filled, it tells the neuron to stop sending DA into cleft
4. (also auto-receptor on presynaptic cleft). Will not transmit message like the rest of the receptors

Question 9

How is serotonin produced?

Answer 9

1. Precursor to serotonin is tryptophan (turkeys-makes you tired)
2. Tryptophan transporter brings tryptophan to serotonin neuron, drops it off and TRYOH enzyme (tryptophan hydrocolase) converts tryptophan to 5HTP (5-hydroxyl-tryptophan), AAADC enzyme (aromatic aa decorboxolate) breaks down 5-HTP into 5-HT (serotonin)
3. Serotonin is packaged into vesicles and stored. VMAT-2 is the pump that picks it up and carries to vesicles

Question 10

How is serotonin destroyed?

Answer 10

1. SERT- transporter that picks up leftover Serotonin in cleft and carries it to cell and drops it off (reuptake),
2. VMAT-2 picks it up inside cell and carries it to vesicles for storage
3. MAO-A inside cell breaks down leftover serotonin that did not get repackaged
4. MAO-B is extracellularly and destroys serotonin

Question 11

Where/What are serotonin receptors?

Answer 11

1. 5ht1d presynaptic auto receptor: gets filled and tells neuron to stop putting out serotonin (on presynaptic terminal)
2. Pre-synaptic 5ht1a auto receptors: located at the somatic dendritic area (on cell body). When serotonin binds to that receptor it causes a shut down of the impulse, slows electrical impulse
3. Alpha-2 hetero-receptor: located on axon terminals of serotonin neuron. When unoccupied by NE, serotonin is released (serotonin brake)
4. Alpha-1 receptor: located on somatic dendritic area of serotonin neuron. When unoccupied by NE, some serotonin is released BUT when occupied by NE a lot of serotonin is released. (Serotonin accelerator)

Question 12

Where does 5-HT have effect in brain?

Answer 12

• frontal cortex: mood
• basal ganglia: agitation, ocd
• limbic: anxiety
• hypothalamus: appetite
• sleep center (brainstem): insomnia
• spinal cord: sex dys
• vomiting center (brainstem?): nausea
• gut: cramps, diarrhea