Principles of Neurotransmission

Question 1

What is a classical neurotransmitter?

Answer 1

it is synthesised in synaptic terminal. Enzymes are synthesised at RER and there is axonal transport of enzymes to terminal.

Question 2

What is an atypical neurotransmitter?

Answer 2

Peptide structure - proteins are synthesised in the NUCLEUS, normally precursors that are cleaved by proteolytic enzymes to make the peptide hormone EG POMC (proopriomelanocortin) - cleaved into ACTH, MSH, CLIP etc

Question 3

List the 3 neurotransmitter classes

Answer 3

Classical - synthesised at terminal
Atypical - peptide
Gases - Nitric oxide

Question 4

What is Sildenafil? How does it work?

Answer 4

Viagra! acts by inhibiting PDES, the enzyme that breaks down cAMP (the effector molecule of NO). NO stimulates GC –> cAMP –> NO –> vasodilation –> erection.
Sildenafil stops the reduction of cAMP.

Question 5

2 ways Ca++ increased in synaptic knob

Answer 5

1. Calcium channels

2. ER release - phospholipase C –> PIP –> Ca++ release from ER

Question 6

What causes the docking of the synaptic vesicle with membrane

Answer 6

Called SNARE proteins - they mediate vessicle fusion:

Presynaptic:
Synaptobrevin, Synaptotagmin

Postsynaptic:
Syntaxin, SNAP-25

Question 7

How does botulism and tetanus act on neurotransmitter release - answer on molecular level

Answer 7

Botulism cleaves SNARE proteins, Ach cannot be released. Used also as botox
Tetanus toxin travels up the axon, reaches spinal cord where the neuron originals from, and acts on the GABA INHIBITORY neurons (blocking Gaba release) thus BLOCKING INHIBITION of motor neurons = contraction.

Question 8

Name 3 ways in which a neurotransmitter is removed from a cleft

Answer 8

Reuptake
Diffusion - peptides will diffuse
Enzymatic degradation

Question 9

Discuss action time of classical vs atypical

Answer 9

Classical- v. short time to act

Atypical - peptides longer time, can diffuse further.

Question 10

What is the most efficient way to interrupt signal of classical neurotransmitters?

Answer 10

Reuptake

Question 11

Discuss the location of the receptors for neurotransmitters

Answer 11

For axo-axonic - there are 2 kinds:

• post synaptic
• presynaptic (auto and heteroreceptors)

Question 12

Discuss autoreceptors

Answer 12

Regulate the synthesis and release of neurotransmitters. Only one neurotransmitter (Noradrenaline) can act on both post synaptic receptors and presynaptic (alpha2) receptors for adrenaline. Can act as negative feedback inhibiting further release of NE.

Question 13

What mechanism can you use to increase the function of a neurotransmitter? [6]

Answer 13

1. increase synthesis
2. decrease storage in vessicles
3. increase release
4. block reuptake
5. inhibit degradation enzyme
6. use agonist for receptor

Question 14

How do you affect neurotransmitter storage?

Answer 14

Reserpine - a drug that blocks VMAT (which normally carries NE into the vessicle)

Question 15

What is reserpine? Why can’t it be used as antihypertension?

Answer 15

A drug that blocks VMAT and stops neurotransmitter storage into vessicles. If you block storage of neurotransmitter in brain = depression

Question 16

What drug do you use for Parkinsons

Answer 16

Levadopa- precursor to dopamine

Question 17

What is Fluoxitine?

Answer 17

Selective serotonin reuptake inhibitor (like Fluvoxamine),which increases serotonin function and has antidepressant action.

Question 18

What does Cocaine do?

Answer 18

Blocks reuptake of noradrenaline in the periphery and dopamine in the brain = stimulation.

Question 19

What does amphetamines do

Answer 19

Blocks reuptake of dopamine and noradrenaline, also blocks Monoaminoxidase (responsible for degrading dopamine, serotonin and noradrenaline)

Question 20

When would we use an AchE INHIBITOR therapeutically

Answer 20

Alzheimers because Ach is important for cognitive function.

Question 21

What is cotransmission - give examples of each in terms of parasympathetic and sympathetic.

Answer 21

release of more than one neurotransmitter at the same time from same terminal:
Parasympathetic: Ach classic, NO classical /VIP (vasoactive intestinal peptide = vasodilator)
Sympathetic: ATP (classical), NA (classical), NPY = neuropeptide Y = increases motivation to eat.

Question 22

Explain SSV and LDV

Answer 22

Small light vessicles (clear vessicles) contain classical neurotransmitter. They have low affinity, so need to be close to the calcium channel.

Large dense core vesicles = peptide.

For classical you need one low frequency stimulation, but for peptide you need high frequency.

SSV is close to presynaptic, activated by voltage gated Ca++ channels
LDCV are more distant and have higher affinity. At dendrites you also have ER Ca++ release.

Question 23

Discuss the three mechanisms of cotransmission / neuromodulation

Answer 23

• potentiation / cooperation
• inhibit each other / antagonise
• point to point / vs distant

Question 24

Which 2 peptides are released from dendrites?

Answer 24

• oxytocin - affecting brain function if released from dendrites.
• vasopressin (ADH)
  Both produced in hypothalamic neurons and normally secreted in posterior pituitary.

Question 25

What is the effect of administration of alpha-MSH

Answer 25

dendritic release of oxytocin, reducing secretion from posterior pituitary, inhibiting firing rate.

Question 26

Functions of oxytocin

Answer 26

Lactation, uterine contractions, but also bonding behaviour, affiliative social behaviours etc.

Question 27

What is neurotransmitter switching?

Answer 27

One kind of neuron can switch the type of neurotransmitter that is makes according to changes in environment. Eg: Hypothalamus is concerned with interaction with environment. Neuron can switch from dopamine to somatostatin (GHIH) production depending on condition. Eg mouse in the dark example.