Receptors and other drug targets

Question 1

Receptor superfamilies

Answer 1

4
distinguished by how they transduce a signal

Question 2

ion channel receptors mechanism of signal transduction

Question 3

ion channel receptor location

Answer 3

in cell membrane

Question 4

ion channel effector protein(s)

Answer 4

channel

Question 5

ion channel time scale of action

Answer 5

milliseconds

Question 6

ion channel agonists

Answer 6

neurotransmitters, in the case of no neurotransmitters channel is closed

Question 7

ion channel drug target

Answer 7

nicotinic acetylcholine receptor

Pancuronium, a nicotinic acetylcholine receptor antagonist, is used to produce paralysis
during anaesthesia

Causes ion to flow into cell

Question 8

G protein-coupled receptors - mechanism of signal transduction

Answer 8

Drug binds to extracellular portion of G-protein, causing a change in cell function via the intracellular portion - affecting enzymes and channels

G proteins link GPCRs to effector proteins a nd enzymes that generate intracellular
second messengers

Question 9

G protein-coupled receptors - receptor location

Answer 9

in the call membrane
7 transmembrane domains

Question 10

G protein-coupled receptors – effector protein(s)

Answer 10

enzyme or channel

Question 11

G protein-coupled receptors – time scale of action

Answer 11

seconds, fast

Question 12

G protein-coupled receptors – agonists

Answer 12

hormones, slow neurotransmitters

Question 13

Example of G-protein receptor and drug

Answer 13

adrenoceptors,muscarinic acetylcholine receptors

Salbutamol, a
beta-2-adrenoceptor agonist relieves bronchospasm in asthma

Question 14

G proteins

Answer 14

Comprise of three subunits
alpha, beta, sigma

G-alpha proteins are the main class (Enzyme coupled)
1. G-as activates adenylate cyclase
2. G-ai inhibits adenylate cyclase
3. G-aq activates phospholipase C

Question 15

enzyme-linked receptors – mechanism of signal transduction

Question 16

enzyme-linked receptors – receptor location

Answer 16

in the call membrane

Question 17

enzyme-linked receptors – effector protein(s)

Answer 17

enzyme

Question 18

enzyme-linked receptors – time scale of action

Answer 18

minutes, slow

Question 19

Example of enzyme-linked receptors and drug

Answer 19

In diabetes, insulin is used to activate the insulin receptor, reducing blood glucose levels

Question 20

Insulin receptor

Answer 20

Enzyme linked receptor

Insulin is a agonist at the insulin receptor –> signals intracelluular change to uptake glucose –> reducing BGL

Question 21

enzyme-linked receptors – agonists

Question 22

nuclear receptors – mechanism of signal transduction

Answer 22

Drug has to travel through the cell membrane and bind to nuclear receptor, form a drug-receptor complex, this travel into the nucleus to bind to DNA affecting translation/transcription

Question 23

nuclear receptors – receptor location

Answer 23

Intracellularly in the cytoplasm

Question 24

nuclear receptors – effector

Answer 24

gene transcription

Question 25

nuclear receptors – time scale of action

Answer 25

hours, very slow

Question 26

nuclear receptors – agonists

Answer 26

steroid hormones, other factors

Question 27

Nuclear receptor example and target drug

Answer 27

Glucocorticoid drugs such as prednisolone are effective anti-inflammatory agents –> bind to glucocorticoid receptor

Question 28

Explain the role of ion channels as drug targets

Answer 28

Ion channels allow ion to pass through, as a drug target this function will either be increased or decreased

• Blockers physically plug the ion channel
• Modulators bind to accessory sites and modulate channel activity

Question 29

Explain the role of enzymes as drug targets

Answer 29

• Substrate analogues competitively inhibit the enzyme (present as endogenous substance)
• Some drugs act as false substrates for enzymes to produce abnormal metabolite
• Pro-drugs must be enzymatically converted to become active does this via enzyme

Question 30

Explain the role of transporters as drug targets

Answer 30

• Specific carrier proteins transport ions and small organic molecules
  across cell membranes
  – glucose, amino acids, neurotransmitters, Na
  +, Ca2+ etc.
• Some drugs inhibit transporters
  – anti-depressant drug fluoxetine inhibits the re-uptake of the neurotransmitter
  serotonin into neurones
• False substrates
  – CNS stimulant amphetamine uses the noradrenaline transporter to enter nerve
  terminals and replace/release the neurotransmitters noradrenaline and serotonin