lecture 6 - drug targets

Question 1

what is the only exception to proteins as target sites

Answer 1

DNA, on which a number of antitumour and antimicrobial drugs act

Question 2

process of neurotransmission

Answer 2

1. neurotransmission synthesis
2. neurotransmission release
3. action on receptors
4. inactivation

Question 3

neurotransmitter synthesis

Answer 3

1. choline taken up in pre-synaptic nerve terminal via choline transporter
2. ChAT synthesizes ACh
3. ACh packed into seminal vesicles by vesicular ACh transporters

Question 4

neurotransmitter release

Answer 4

1. vesicles held in cytoskeleton by Ca2+ sensitive vesical membranes proteins (VAMPs)
2. AP reaches pre-synaptic terminal opening voltage-gated Ca2+ channels
3. influx of Ca2+ causes vesicular fusion

Question 5

define receptors

Answer 5

proteins which specifically recognise a particular neurotransmitter/hormone and upon binding undergo a conformational change elading to activation/inhibition of cell signaling

Question 6

name the four main families of receptors

Answer 6

• ligand-gated ion channels
• G-protein coupled receptors
• tyrosine kinase/cytokine receptors
• nuclear/steroid hormone receptors

Question 7

Vascular endothelial growth factor receptors (VEGFR)

Answer 7

• essential for angiogenesis during development, pregnancy, wound healing
• also in pathophysiological conditions e.g. cancer
• multiple receptors/multiple ligands
• tyrosine kinase receptor

Question 8

VEGFR 2

Answer 8

receptor activation leads to activation of PLCγ
• PLCγ hydrolyzes PIP2 —> DAG + IP3
• DAG activates PKC, which leads to activation of Raf, MEK, ERK
• altered gene transcription by ERK

Question 9

examples of G protein coupled receptors

Answer 9

opioid, adenosine, dopamine, serotonin, muscarinic, cannabinol receptors

Question 10

Binding of drugs to receptors (in order of increasing strength)

Answer 10

• Van der Waals forces
• Hydrogen bonding
• ionic interactons
• covalent binding (essentially irreversible)

Question 11

Serotonin (5HT)

Answer 11

• 5HT/serotonin involved in sleep, appetite, memory, sexual behaviour, neuroendocrine function,
mood
• synthesised from tryptophan (trp), released from vesicles during AP