Adrenergic Pharmacology

Question 1

What is the rate limiting enzyme in the pathway of adrenergic synthesis?

Answer 1

Tyrosine Hydroxylase (converts Tyrosine to L-DOPA)

Question 2

How is NA stored in the synaptic terminal?

Answer 2

Within a vesicle, it’s stored with ATP and protein chromogranin A. The VMAT2 allows NA entry using a proton gradient

Question 3

Name the drug which blocks the VAMT2 transporter?

Answer 3

Reserpine.

Question 4

What is the effect of Tyramine?

Answer 4

It reverses the direction of transport of VMAT2 which results in the increase of NA and DA in the cytosol
It is also a competitive blocker of MAO

Question 5

Describe the Uptake 1 Adrenergic mechanism

Answer 5

This is the neuronal uptake pathway. NA has a higher affinity for this route. It is taken up by NET on the presynaptic membrane; NET is a co transporter of Na+ and Cl-

Question 6

What is the effect of cocaine on adrenergic transmission?

Answer 6

Blocks NET so NA has a prolonged effect in the synapse

Question 7

Describe the Uptake 2 Adrenergic mechanism

Answer 7

This is the extra-neuronal uptake pathway. Adrenaline has a higher affinity for this. The EMT transporter clears the adrenaline from the blood.

Question 8

What is the significance of vanillyl mandelic acid (VMA)and adrenergic metabolism?

Answer 8

The action of MAO and COMT on NA produces VMA. high levels of VMA in the urine is indicative of a tumour of the chromaffin tissue

Question 9

Where in the cell is MAO found?

Answer 9

On the outer mitochondrial membrane of cells.

Question 10

Name the inhibitors of MAO and COMT. State their uses.

Answer 10

MAO is inhibited by Phenelzine and Selegiline, which is used for PD treatment
COMT is inhibited by Tolcapone which is used for PD treatment.