Catecholamines I

Question 1

Synthesis of Catecholamines.

Steps from Tyrosine–>DOPA?

Answer 1

Use of Tyrosine Hydroxylase.

Adds OH to Tyrosine to create DOPA.

Question 2

DOPA—> Dopamine?

Answer 2

Aromatic amino acid decarboxylate(AADC).

Question 3

Dopamine–> Norepinephrine.??

Answer 3

Dopamine B-hydroxylase.

• Additional oxygen creating hydroxyl group.

Question 4

State the overall synthesis steps from Tyrosine to Norepinephrine.

Answer 4

Tyrosine—> DOPA( tyrosine hydroxylase)

DOPA—> Dopamine( aromatic amino acid decarboxylase)..

Dopamine—> norepinephrine.( Dopamine B-hydroxylase).

Question 5

State the rate enzyme of this synthesis.

Answer 5

Tyrosine Hydroxylase(TH).

Question 6

2 factors of regulating TH which in turn influence Catecholamine synthesis,

Answer 6

1. High level of Catecholamines:
   
   • inhibit TH: creating a negative feedback.
2. Rate of cell firing:
   
   • TH is stimulated, accelerating catecholamine synthesis.

Question 7

Function of L-DOPA in catecholamine synthesis?

Who would it be targeted to?

And why?

Answer 7

Accelerates Catecholamine synthesis.

Individuals with Parkinson’s, as it increases levels of Dopamine.

Question 8

Function of AMPA and what does it stand for.

Answer 8

α-methyl-para-tyrosine.

• Blocks tyrosine and stops catecholamine synthesis.

Question 9

What is the name of this and state its function as it is attached to the synaptic vesicles?

Affect of reserpine?

Answer 9

Vesicular monoamine transporter(VMAT).

• Recognises monoamines and transports them in order for exocytosis from the presynaptic terminal.

Reserpine:

• Blocks VMAT, preventing entry of monoamines entering vesicles.

Question 10

2 drugs which can cause independent cell firing.

Answer 10

Amphetamines and Methamphetamines.

Question 11

Results of higher doses of amphetamines and methamphetamines.

Why does this occur?

Areas in the brain this occurs?

Overall [5 marks].

Answer 11

Stereotyped movement.

• Intense sniffing.
• Repetitive head movements and limbs.
• licking and biting.

Increased stimulation of DA receptors.:

in striatum and nucleus accumbens.

Question 12

The function of Autoreceptors.

Overall cellular change?

and the result?

Function of somatodendritic auto receptors.

Answer 12

• Inhibits catecholamine release.
• Enhances of K+ channel opening.
• Reduces Ca2+ influx, therefore reducing vesicle exocytosis.

Somatodendritic autoreceptors: inhibiting neurotransmitter release.

reducing rate of firing cell.

Question 13

Result of mutant mice with no D2 autoreceptors:

State also the NE autoreceptors.

Answer 13

Are more active and more sensitive to cocaine.

Ne autoreceptors: alpha2 subtype.

Question 14

The function of Alpha2-agonist?Clonidine?

The function of Alpha2-antagonist?yohimbine?

Answer 14

Clonidine:

• used to treat withdrawal symptoms from opioid drugs activating noradrenergic system.

Yohimbine:

• blocks autoreceptors.
• increase noradrenergic cell firing.
• Increase NE release.

Question 15

State examples of the importance of Transport medium uptakes in the regulation of catecholamine activity.

Answer 15

Studies in:

• Removal of DA transporters:
  
  • Do not respond to psychostimulants like cocaine.
• Removal of NE transporters.
  
  • Increase sensitivity to psychostimulants.

Question 16

Examples of Transporter blocking drugs and what transporter they block?

Answer 16

• Tricyclic antidepressant:
  
  • inhibits the reuptake of NE and serotonin.

Robeoxetine: Antidepressant.

• blocks reuptake of NE/

Atomoxetine:ADHD:

• Blocking NE transporters/.

Question 17

The effects of Cocaine.

Answer 17

• Blocks all monoamine transmitters:
  
  • DA. NE and 5-HT

Question 18

Metabolites of DA in humans?

Answer 18

Homovanillic acid.

Question 19

NE metabolites in humans?

Brain?

PNS?

Answer 19

• Brain:
  
  • MHPG: 3-methoxy-4-hydroxy-phenylglycol.
• PNS:
  
  • Vanillymandelic acid(VMA)..

Question 20

Examples of MAO inhibitors?

function?

Answer 20

Phenelzine and Tranylcypromine.

• Treatment of clinical depression.

Question 21

Function of COMT inhibitors and list 2.

Answer 21

Entacapone and Tolcapone.

• enhances the effectiveness of L-DOPA, as it prevents the breakdown of DOPA.

Question 22

State the 2 cell group divisions for DA neurons and NE neurons.

Answer 22

NE neurons:

• A1-A7.

DA neurons:

• A8-16.

Question 23

State the A9 cell group and tract involved.

Answer 23

A9 cell group within Substantia nigra.

• The nigrostriatal tract:
  
  • Substantia nigra—–> straitum or caudate putamen.

Question 24

State the A10 cell group and the 2 pathways which branch off it.

Answer 24

The ventral tegmental area(VTA).

• Mesolimbic pathway: VTA—> limbic component
  
  • e.g.: nucleus accumbens,
• Mesocortical pathway: VTA—> pre-frontal cortex.
  
  • e.g.: hippocampus or anterior olfactory nucleus.

Question 25

Function of the nigrostriatal pathway? consequence of PD to this pathway?

Answer 25

* **Facilitates voluntary movement**. **_Parkinson's_**: * *loss of neurons in the substantia nigra*. * * *Denervations of the striatum*.

Question 26

The difference in function between D1 like receptors and D2 like receptors?

Answer 26

**D1 like receptors**: * Activation **stimulates** adenylyl cyclase and *synthesis of cAMP*. **D2 like receptors**: * Inhibits adenylyl cyclase and synthesis of cAMP. * Regulates K+ channels. * K+ channel *_decreases excitability_* and *_decreases cell firing_*.

Question 27

State NE neuron cell groups. location. State the area of where the fibres extend?

Answer 27

* **_A6_** neuronal NE cell group. ***_Pons_***. * ***Locus Coeruleus***. * Fibres extend to the **forebrain**, **cerebellum** and the **spinal cord**.

Question 28

How does the peripheral part of the NE system work. Two possible ways of travel?

Answer 28

*_Sympathetic nervous systems_* with fibres extending to various organs. * Sympathetic noradrenergic neurons have **synapse-like** contact. OR * Released into the bloodstream via the release **from adrenal glands**.