Synaptic Transmission

Question 1

5 steps in neurotransmission

Answer 1

1) nt synthesis
2) vesicular storage
3) synaptic release
4) binding to receptor
5) termination of transmission

Question 2

nt synthesis requires…. (and which are common sites of drug action?)

Answer 2

• precursors*
• transport into the cell (not specific enough to target with drugs)
• enzymatic action*
• = common sites of drug action

Question 3

vesicular storage drug target

Answer 3

-inhibit vesicular transport to keep nt in the cytoplasm where it will then be degraded by enzymes

Question 4

what nts aren’t stored in a vesicle

Answer 4

gases and some nucleosides

Question 5

synaptic release involves… (and which are sites of drug action)

Answer 5

• AP propagated to terminal*
• opens Ca channels
• fusion of vesicle with the mb*

*drug targets

Question 6

snare proteins

Answer 6

• enable calcium dependent docking of vesicle with pre-synaptic mb
• enable exocytosis of nt

Question 7

BoTox

Answer 7

• endocytosed into cholinergic neurons
• degrades SNAREs
• prevents calcium-dependent exocytosis of nt

Question 8

indirect acting drugs

Answer 8

facilitate the incr of nt in synapse

Question 9

amphetamine

Answer 9

• has affinity for monoamine reuptake transporters
• leads to transporter p-lation
• probably also inhibits vesicular uptake proteins
• reversal of transporter - spews nt out
• calcium-independent release of nt

Question 10

nts can bind receptors on…

Answer 10

both the pre- and post- synaptic mbs

Question 11

Glutamate termination of nt action

Answer 11

-transporter into glial cell and post-synaptic neuron (it doesn’t have its own pre-synaptic neuron)

Question 12

monoamine termination of nt action

Answer 12

VMT2 in presynaptic neuron

Question 13

choline termination of nt action

Answer 13

-VACht channel in pre-synaptic neuron

Question 14

GABA termination of nt action

Answer 14

VGA in presynaptic terminal, glial cell, and post synaptic neuron

Question 15

tyrosine hydroxylase

Answer 15

-rate limiting enzyme in the conversion of Tyrosine to DOPA

Question 16

metyrosine

Answer 16

• will preferentially bind tyrosine hydroxylase but it won’t make DOPA so you just decrease its production
• doesn’t cross BBB where most DA neurons are , so this mainly affects NE neurons so the overall effect is to decr BP

Question 17

reserpine

Answer 17

• it blocks vesicular monoamine transporter (VMT) which takes DA up into cells where it would be converted to NE.
• DA will then stay in the cytoplasm and get degraded
• if you give this in big enough doses, it will cross the BBB and people will get depressed because they won’t have enough DA

Question 18

selectivity of drug action on the manipulation of nt release is dependent on …

Answer 18

access to the target cell type

Question 19

Bretylium

Answer 19

has a selective affinity for NE transporters