Drug Targets 1 Receptors And Enzymes

Question 1

What are the potential targets for drugs

Answer 1

Receptors
Ion channels
Enzymes
Transporters

Question 2

Describe the potential target (receptors) for drugs

Answer 2

Receptors are located at the cell surface and within the cell. An agonist increase the activity of a receptor above its basal level whereas an inverse agonist decreased tbe activity below the basal level.
The agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response which can be direct such as the ion channels open and close or through transduction mechanisms which is when the enzyme activation/inhibition, ion channel modulation and DNA transcription happens.
Antagonist blocks the action of the agonist which causes no effect and the endogenous mediators are blocked

Question 3

Describe the potential target (ion channels) for drugs

Answer 3

There is a channel blocker and channels modulator.
Channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell.
Channel modulators increase or decrease opening probability.

Question 4

Describe the potential target ( enzymes) for drugs

Answer 4

Drug binds to an inhibitor and then it makes a normal reaction
False substrate- abnormal metabolite produced
Prodrug- active drug produced

Question 5

Describe the potential target ( transporters) for drugs

Answer 5

The agonist/ substrate binds to tbe transporters and then it’s a normal transport.
When an inhibitor binds to transported the transport is blocked so agonist cannot bind.
When false substrate binds then it’s an abnormal compound accumulated

Question 6

Describe cellular signalling

Answer 6

Central to multi cellular organisms.
Evolved before multi cellular life.
Requires low conc of agonists- <10-8M ie Ka > 108 I/m.
>1500 Gene’s encode cell receptor proteins.
Highly conserved families of receptor proteins.

Question 7

Describe the activation of cell surface receptors

Answer 7

1) receptor-ligand binding ( ligand( primary messenger) binding onto the receptor)
2) signal transduction (via second messengers)
3) cellular responses
4) change in gene expression
- also signal transduction is required for cellular response in this activation.

Question 8

Do 4 5 8 9 10

Answer 8

…

Question 9

What are the types of cell surface receptors

Answer 9

• Ion channel coupled
• G-protein coupled (GPCR)
• enzyme coupled

Question 10

Are nuclear receptors intracellular or extracellular

Answer 10

Intracellular

Question 11

Give examples of drug acting via nuclear receptors

Answer 11

• glucocorticoids ( inhibits NF- kB
• modulates gene expression in immune cells
• anti-inflammatory
• side effects

Question 12

Define receptors

Answer 12

Cell signalling

Question 13

What does cellular signalling require

Answer 13

Requires low conc of agonist <10-8 M

Question 14

How many Gene’s encode cell receptor proteins

Answer 14

1500 Gene’s encode cell receptor proteins

Question 15

What is the process of cellular response

Answer 15

1. Receptor - ligand binding
2. Signal transduction (2nd messenger)
3. cellular response
4. Gene expression

Question 16

2 types of cell signalling can produce ….

Answer 16

Distant or local

Question 17

Why do agonists and drug bind to receptors

Answer 17

To produce an effect

Question 18

What are the three types of cell surface receptors

Answer 18

Ion channel coupled
G protein coupled (GPCR)
Enzyme coupled

Question 19

What are the 4 types of receptor effective linkage

Answer 19

1. Ligand gated ion channels
2. G protein coupled receptors
3. Kinase linked receptors
4. Nuclear receptors

Question 20

Describe the process of ligand gated ion channels (ionotropic receptors) include time scale and examples

Answer 20

Time scale - milliseconds
Examples - nicoinic ACh receptors
Process- ligand gated ion channels are integral membrane proteins that contain a pore which allows the flow of selected ions across the plasma membrane.ligand gated ion channels bind to neurotransmitters and open in response to ligand binding. It allows ions to diffuse down their electrochemical gradient. This then results in hyper polarisation for inhibitory response or depolarisation for excitatory receptor response

Question 21

Describe the process of G protein coupled receptors ( metabotropic) and include time scale and example

Answer 21

Time scale- seconds
Examples- muscarinic ACh ACh receptor
Process- GPCR interact with G proteins in plasma membrane when an external signalling molecule binds to a GPCR it caused a conformational change in the GPCR. This change then triggers the interaction before the GPCR and a nearby G protein. This releases Ca2+ and the change causes cellular effects.
The second messenger causes protein phosphorylation which also causes cellular effects.

Question 22

Describe kinase linked receptors and include time scale and examples

Answer 22

Time scale - hours
Examples - cytokine receptors
Process- kinase linked receptors is a transmembrane receptor which uses second messenger signalling that triggers a cascade of cellular events. Ligands bind to the receptor binding site at the extracellular domain whixh causes phosphorylation of amino acids within intracellular domain. This then causes gene transcription then protein synthesis and this then has a cellular effect.

Question 23

Describe the process of nuclear receptors and include time scale and examples

Answer 23

Time scale - hours
Examples - oestrogen receptor
Process-nuclear receptors are activated by lipid soluble signals that cross the plasma membrane. Once activated most function as transcription factors to control gene expression, protein synthesis and then causes a cellular effect.

Question 24

What are the G protein coupled receptors 2nd messengers

Answer 24

• cAMP
• Ca2+
• Inositol 1,4,5- triphosphate
• Diacylglycerol

Question 25

What does signal transduction do

Answer 25

Amplifies the cellular response

Question 26

Give some drug target for G protein coupled receptors

Answer 26

-B-adreneegic receptor 
Gs coupled receptor 
Sub classes have tissue specific expression 
B1 heart B 2 smooth muscle 
Activation fight or flight 
Antagonist B blockers 
Propranolol first synthesised

Question 27

Example of drug acting via enzyme

Answer 27

Aspirin inhibits 1 enzyme function

Question 28

What are effects of aspirin

Answer 28

Acetylsalicylic acid ( aspirin) 
Aspirin inhibits the function of one enzyme

Question 29

Describe the action of anti inflammatory drugs

Answer 29

So cyclooxygenase is inhibited by aspirin, ibuprofen so its blocks the effects of natural chemicals called cyclooxygenase enzymes (COX). these enzymes help make other chemicals in the body called prostaglandins. Postagladins are produced at site of injury and cause pain and inflammation.
Add more look at diagram……

Question 30

Examples of intracellular signalling pathways

Answer 30

Nitric oxide via 2nd messenger (cGMP)

nuclear receptors

Question 31

Nitric oxide 
How is it reversed ?
Physiological effects ?
Drug interactions ?
Effect of Ach is dependent on the target cell ?

Answer 31

…

Question 32

What is the mechanism of sildenafil ?

Answer 32

….

Question 33

What does sildenafil inhibit

Answer 33

Inhibits the phosphodiesterase that destroys cGMP

Question 34

Examples of drugs acting via nuclear receptors

Answer 34

Glucocorticoids (inhibits NF - kB)
Modulates gene expression in immune cells
Anti inflammatory
Side effects

Question 35

Activation of cell surface molecules 2

Answer 35

Extracellular signal molecule binds to its receptor and changes its intracellular portion and that will have an affect on the proteins that will already express in the cell and that can occur really quickly.
Or it can have an affect on altered protein synthesis which is much slower and long living

Question 36

Signalling molecules

Answer 36

2 ways signalling molecules work - act in distance from where they release and (1)
agonist that will only act on cells that are close to them.(2)
Hormones - will get into the bloodstream and be distributed around the body and target distance cells.(1)
Local mediators - unstable molecule so will only diffuse two far and then lose their functionality.(2)