L14 - What Is A Receptor: Types And Functions

Question 1

What are the main protein targets for drug action?

Answer 1

• receptors
• ion channels
• enzymes
• transporters

Question 2

What are ion channels?

Answer 2

Allow passafe of channel-specific ions down a conc grad
- open in response to environmental cue
- present on membranes

Question 3

What are the types of drugs that act on ion channels?

Answer 3

• blockers
• modulators

Question 4

What do blockers do at ion channels? Eg?

Answer 4

Blocks channel - prevents ion movement
- lidocaine, blocks VG Na+ channels

Question 5

What do modulators do at ion channels?

Answer 5

Increases/decreases chance of channel opening
- gabapentin - reduces activity of VG Ca+ channels

Question 6

What do enzymes mediate? And act as?

Answer 6

• mediate biochemical signals within cells and tissue
• act as biological catalyst accelerating chemical reactions

Question 7

What are the types of drugs that act on enzymes?

Answer 7

• inhibitors
• false substrates
• prodrug

Question 8

What are transporters (carrier proteins)?

Answer 8

Transport substances across membranes against a conc grad (active transport)
- doesn’t open to both sides, actively moves substance

Question 9

What type of drugs that act on transporters?

Answer 9

• inhibitors
• false substrates

Question 10

What do inhibitors do at transporters? Eg?

Answer 10

Block the transport of substances
- fluoxetine, serotonin transport blocker

Question 11

What do false substrates do at transporters?

Answer 11

Abnormal compound accumulates
- amphetamine, acts on dopamine and noradenaline transporters

Question 12

What do inhibitors do at enzymes? Eg?

Answer 12

Prevents activity
- aspirin, cycloozygenase inhibitor

Question 13

What do false substrates do at enzymes? Eg?

Answer 13

Abnormal metabolite produced
- fluorouracil, chemotherapy

Question 14

What do prodrugs do at enzymes? Eg?

Answer 14

Activation of drug molecule
- codeine, converts to morphine

Question 15

What are receptors?

Answer 15

Proteins that respond to exogenous cue and realy signal into a cell to produce a response
- allow fine tuning of physiological function

Question 16

What type of drugs act on receptors?

Answer 16

• agonist
• antagonist
• modulator

Question 17

What do agonists do at receptors? Eg?

Answer 17

Activate the receptor
- morphine, activates opioid receptors

Question 18

What do antagonists do at receptors? Eg?

Answer 18

Block the receptor, endogenous activators unable to bind
- naloxone, blocks opioid receptors

Question 19

What do modulators do at receptors? Eg?

Answer 19

Increases/decreases receptor activation
- diazepam, enhances GABA receptor activation

Question 20

What is the definition of a ligand?

Answer 20

Something that binds
(Doesn’t imply any activity)

Question 21

What is the definition of an agonist?

Answer 21

Something that binds and produces a response

Question 22

What is the definition of an antagonist?

Answer 22

Somethings that binds and produces no response

Question 23

What is the definition of second messenger?

Answer 23

Relay signal from receptor to effector within cells

Question 24

What is the definition of a signal transduction?

Answer 24

Sequence of second messengers that elicit a biological response

Question 25

Basics of ligans-receptor interactions:

Answer 25

• ligand binds to receptor = conformational change of receptor protein
• cellular effect (opening of channel, activation of linked enzyme, recruitment of effector protein, intracellular transport)

(Signal - action - response)

Question 26

What are the 4 main families of receptors?

Answer 26

• ligand gated ion channels
• g protein coupled receptors
• kinase linked receptors
• nuclear receptors

Question 27

What are ligand gated ion channels? Eg?

Answer 27

Channels that open in response to ligand binding
- allwos movement of channel-specific ions

• Ach and NAch receptors

Question 28

What are the steps in Ach and Nicotinic receptors?

Answer 28

• electrical impulse travels down pre-synaptic neuron
• triggers release of Ach
• Ach acts on nAChRs on post-synaptic neuron
  = opens channels, influx of Na+ = impulse

Question 29

What is kinase? What does it act as?

Answer 29

• enzyme - phosphorylates target
• acts as swicth
• turns target on/off
• allows other 2nd mes to bind

Question 30

What are receptors like in kinase-linked receptors? What happens?

Answer 30

• two halves in the membrane (monomer)
• ligand-receptor engagements bring two together (dimer)

= activates kinase activity of receptor
= downstream cascade/biological response

Question 31

Eg of kinase linked factor:

Answer 31

Epidermal growth factor receptor (EGFR)
- promotes cell growth
- more EGFR = more growth

Question 32

What are G protein coupled receptors? What happens?

Answer 32

Receptor with 7 transmembrane domains, coupled to G protein
- ligand binding activates G proteins = interacts with effector

Question 33

What are the steps in GPCR activation?

Answer 33

• resting state
• ligand binds, GDP -> GTP
• GTP bound G protein interacts with effector = biological response
• GTP hydrolysed, G protein dissociates from effector

Question 34

Eg for GPCR:

Answer 34

Muscarinic M3 GPCRs (on intestinal smooth muscle)
- activation = contraction (peristalsis)
- antimuscarins used for IBS

Question 35

What are nuclear receptors? What happens?

Answer 35

Receptor no associated with cell membrane
- ligand enters cells, bind to receptor in cytoplasm
- ligand-receptor complex moves to nucleus
= acts on gene expression

Question 36

Eg for nuclear receptors:

Answer 36

Oestrogen receptor
- important for secual maturation, gestation
- more oestrogen receptors = more growth = cancer
- susceptible to targeted therapy (tamoxifen)