Neurotransmission and Drug Mechanisms

Question 1

Describe how a signal is conducted across a synapse

Answer 1

1) Synthesis of NT in pre-synaptic neurone
2) Packed into vesicle
3) AP permits movement and fusing of vesicle to pre-synaptic membrane
4) Exocytosis into synaptic cleft - binds to receptor
5) Initiates signalling cascade downstream causing cellular response
6) Termination - enzyme breaks NT into metabolites

Question 2

Define the roles of GLUTAMATE & GABA
What do they cause?
How are they changed?

Answer 2

Glutamate - excitatory NT (increased depolarisation via Na+). Changed to glutamine in glial cells via glutamine synthase
GABA - inhibitory NT (hyperpolarisatoin via cl- influx). Starts as glutamine.
Glutamic acid decarboxylase + pyridoxyl phosphate

Question 3

What is the equation for production of ACh

What is the equation for breakdown of ACh

Answer 3

acetylCoA + Choline (via choline-acetyl transferase)

acetylcholinesterase = acetate + choline

Question 4

Describe production of catecholamines

Answer 4

1)Tyrosine
tyrosine hydroxylase
2) L-DOPA
DOPA decarboxylase
3) Dopamine
dopamine B-hydroxylase
4) Noradrenaline
phenylethanolamine N-methyl-transferase
5) Adrenaline

Question 5

Describe production of indolamines (5-HT)

Answer 5

1) Tryptophan
tryptophan hydroxylase
2) 5-hydroxytryptophan
5-HTP decarboxylase
3) 5-hydroxytryptamine

TERMINATED BY MAO/COMT or REUPTAKE

Question 6

Describe nitric oxide (atypical)
What is it made from?
How is it terminated?
What direction does it travel in?

Answer 6

L-arginine - NO
Not stored in vesicles/diffuses freely
Termination is passive
Can go in either direction

Question 7

How do Inotropic receptors/ Ligand gated ion channels work?
Give examples
What causes activation

Answer 7

nACh, NMDA, AMPA, GABAa
eg diazepam to GABAa
conformation change induces opening of channel
influx of ions (Cl- causing hyper polarisation)
Cellular response

Question 8

How do metabotropic receptors work?
Give examples
How are they activated?

Answer 8

alpha and beta adrenoreceptors
eg noradrenaline to alpha1
G-protein coupled, dissociates B and Y region, GTP links to alpha subunit, links up to adenylate cyclase which increases cAMP which induces a cellular response

Question 9

How Do Tyrosine Kinase associated receptors work?

How are they activated?

Answer 9

6 binding sites that link to phosphate, ligand bonds to each monomer, ATP donates Pi to the receptor.
Forms an activated dimer, relay proteins attach causing a cellular response

Question 10

How are these diseases caused

1) Parkinson’s
2) Anxiety and Depression
3) Alzheimer’s

Answer 10

1) Effect on synthesis of dopamine
2) Effect on storage and release (MAO/COMT)
3) Effect on termination (acetylcholinesterase)

Question 11

What do these drugs target and what are they used for?

1) Triptans
2) antipsychotics
3) opioids
4) benzodiazepines
5) ketamine/PCP
6) nicotine

Answer 11

1) Migraine, 5-HT1 agonist
2) schizophrenia, D2 antagonist
3) pain, u opioid agonist
4) anxiety, GABAa modulator
5) anaesthesia, NMDA antagonist
6) Drugs of abuse, Nicotine agonist