Catecholamines

Question 1

The enzyme required for Tyrosine—–>DOPA??.

Answer 1

Tyrosine hydroxylase.

Question 2

The enzyme required to convert DOPA—->Dopamine??.

Answer 2

Aromatic amino acid decarboxylase(AADC).

Question 3

The enzyme to convert dopamine—–>Norepinephrine??

Answer 3

Dopamine B-hydroxylase.

Question 4

Packaging of catecholamines?

Answer 4

• Achieved via Vesicular monoamine transporter(VMAT).
• released via exocytosis.

Question 5

Functions of;

• Amphetamines?
• Reserpine?

Answer 5

Amphetamines:

• increase cell firing.

Reserpine:

• Block DA uptake in VMAT2,
  
  • results in depression and sedation.

Question 6

• The function of Autoreceptor D2 autoreceptors?

How does it achieve this function?

what type of autoreceptor are they?

Answer 6

Overall function: inhibits catecholamine release.

• Enhances opening of K+ channels, hyperpolarisation.

therefore:

• reduces AP and Ca2+ influx.
• Somatodendritic autoreceptor.

Question 7

The function of transporter proteins?

Answer 7

• Allow the reuptake of NE and DA.

Question 8

Role of Tricyclic antidepressants?

Answer 8

• Inhibit reuptake of both NE and Serotonin.

Question 9

Neurophysiology of cocaine?

Answer 9

• inhibits the reuptake of all mono-amine transmitters:

DA,5-HT, and NE.

Question 10

Function of Roboxetine( edronax)?

Function of Atomexetine(Strattera)?

Answer 10

• Roboxetine : antidepressant, blocking NE transporters(reuptake)
• Atomoxetine (Strattera):
  • Used for ADHD to block NE transporters.

Question 11

The difference in function between Catechol-O-methyltransferase(COMT) AND Monoamine oxidase(MAO)??

Answer 11

COMT: degrades and breakdown dopamine.

MAO: degrade and breakdown of NE.

Question 12

Metabolites of DA and NE??

Answer 12

• DA: Homovanillic acid.
• NE: CNS: MHPG and PNS: VMA.

Question 13

How can levels of catecholamine levels be measured?

Answer 13

• Measuring the levels of metabolites within urine, e.g. Homovanillic acid for DA.

Question 14

Function of Phenelzine(Nardil) and Tranylcypromine(Parnate)?

Answer 14

• Are MAO inhibitors, which inhibit metabolism and breakdown of NE.

Question 15

Function of Entacapone(Comtan) and Tolcapone(Tasmar)?

Answer 15

• inhibition of COMT, inhibits breakdown of DA.

Enhances the functioning of L-DOPA for PD.

Question 16

What cell group classification system correspond to NE and DA?

Answer 16

• NE= A1-A7.
• DA= A8-16.

Question 17

Describe the Nigrostriatal pathway:

• from where—where?
• Cell groups?

Answer 17

• Substantia nigra———-

–>Striatum.

or

–>caudate putamen.

A9 CELL GROUP.

Question 18

Describe the mesolimbic dopamine pathway;

Cell groups and projections?

Answer 18

• A10 cell group.
• VTA——-
  • –> limbic system( Nucleus accumbens and Olfactory tubercules).

Question 19

Describe the mesocortical dopamine pathway.

• Cell group and projections?.

Answer 19

• A10 cell group.
• VTA——–>
• –>prefrontal cortex.

Question 20

State the significance of the nigrostriatal pathway to PD models?

toxins used as a model for PD?

Answer 20

• Fascilitates voluntary movement.
• PD involves the loss of DA neurons from the SN, which leads to denervation of the striatum.

Neurotoxins:

• 6-OHDA and MPTP: damage the nigrostriatal pathway.

Question 21

State the type of receptor DA receptors are.

• Briefly state the mechanism in activation of these receptors?
• State the receptors within D1-like receptors and D2-like receptors.

Answer 21

Metabotropic receptors:

• interacting with G-proteins and function as secondary messengers.

D1-like receptors: D1 and D5.

D2-like receptors: D2-D4.

Question 22

Activation of:

D1 receptors and D2 receptors?

Answer 22

D1 receptors:

• stimulates adenylyl cyclase and synthesis of cAMP.

D2 receptors:

• inhibits adenylyl cyclase and synthesis of cAMP.
• Opening of K+ channels, as activation of G-protein enhances K+ opening.

Question 23

Receptor-selective drugs: AGONISTS.

• Function of:
  
  • SKF 38393.
  • Quinpirole.
  • Apomorphine.

Answer 23

SKF 38393:

• Is an agonist for D1 receptors.

Quinpirole:

• activates D2 and D3 receptors.

Apomorphine:

• agonist stimulating D1 and D2

Question 24

Receptor selective ANTAGONISTS.

Uses and function of Haliporidol and SCH 23390.

Answer 24

Function:

• Suppressor of locomotor and exploratory movement.

Haloperidol; D2 receptor blockers.

SCH 23390: D1 receptor blockers.

Question 25

Mice knockout:

D1 knockout?

D2 knockout?

Both knockout?

D4 knockout?

Answer 25

• D1 receptor knockout: deficits in cognitive tasks.
• D2 receptor knockout: impairment in spontaneous movement, coordination, and posture.

Both: leading to fatality in the 2nd and 3rd week of life.

• D4 receptor knockout: hypersensitive to cocaine and methamphetamines.

Question 26

Quick overview of the drugs.

Answer 26

Question 27

Describe the Locus Coerulus(LC) in pons:

• Group of cells?
• Projections?

Answer 27

• A6 cell group.
• Projections from pons to——-

—> all areas of the forebrain.

—> cerebellum and spinal cord.

Question 28

Describe the adrenoreceptors?

• type of receptor?
• 2 groups.

Answer 28

• Metabotropic receptors:

alpha and beta.

a2: reduces cAMP synthesis.
a1: operates via phosphoinositide second messenger system.

B1 and B2:

• stimulate adenylyl cyclase and enhance cAMP.(like D1 receptors).