Receptors

Question 1

Define affinity

Answer 1

Chemical forces that causes the drug to bind to the receptor site

Question 2

Define efficacy

Answer 2

Extent of functional change imparted to a receptor upon binding of a drug

Question 3

Define potency

Answer 3

Dose of drug needed to produce a biological effect

Question 4

What are receptors?

Answer 4

Macromolecules involved in chemical signalling between and within cells

Question 5

What is an agonist?

Answer 5

Drug that binds to receptors and initiates a cellular response

Mimics something that happens within body

Question 6

What is the affinity and efficacy of agonists?

Answer 6

High affinity - bind strongly to receptors

High efficacy - elicit a huge response

Question 7

What are partial agonists?

Answer 7

Act on same receptor but don’t produce the same maximal response - still fit in with receptors but don’t bind as strongly

Question 8

What are inverse agonists?

Answer 8

Act on same receptor but produces an opposite effect - high affinity but outcome is different to what we want

Question 9

What is an antagonist?

Answer 9

Designed to do the opposite of what’s happening in the body

Drug binds to receptors but doesn’t initiate a cellular response

Question 10

What is the affinity and efficacy of antagonists?

Answer 10

Has affinity but no efficacy

Question 11

What is a competitive antagonist?

Answer 11

Binds to same site as agonist but doesn’t activate it

Question 12

What is a non-competitive antagonist?

Answer 12

Binds to an allosteric site (different site than active site) to prevent activation of receptor by changing structure completely

Question 13

What are the 4 types of receptors?

Answer 13

1. Internal/nuclear receptors
2. Cell surface receptors / Receptors kinases
3. Ion channel-linked receptors
4. G-protein coupled receptors

Question 14

How do ion channel-linked receptors work?

Answer 14

Ion channel-linked receptor binds to ligand and open a channel through the membrane that allows specific ions to pass through

Ligand binds to extracellular receptor site, causing a structural change and the ion channel will open

Question 15

Where does an ion channel-linked receptor sit? How does it form a channel?

Answer 15

Cell surface receptor

Has extensive membrane spanning region (transmembrane) –> 5 transmembrane subunits

Question 16

What is an example of an ion channel-linked receptor?

Answer 16

Neurotransmitter

Question 17

What is a G-protein coupled receptor?

Answer 17

Single polypeptide chain that threads across cell membrane 7 times (7 transmembrane units). GPCRs interact with G-proteins in membrane.

Ligand binds to extracellular binding sites

Question 18

How do GPCRs work?

Answer 18

1. Ligand binds to GPCR
2. Causes conformational change in GPCR
3. Triggers activation of G protein
4. GTP displaces GDP
5. Active G protein binds to enzyme causing cellular response
6. GTP is hydrolysed into GDP, causing enzyme to release G protein and reaction stops

Question 19

What are second messengers?

Answer 19

Intracellular signalling molecules that are released in response to exposure to first messengers (extracellular signalling molecules) –> activation of single G-rptoein can affect production of 1000s of 2nd messenger molcules

Question 20

What are some examples of 2nd messenger molecules?

Answer 20

cAMP, DAG, IP3

Question 21

What is function of 2nd messengers?

Answer 21

Allow signal conduction to be amplified

Question 22

What are examples of enzymes that produce 2nd messengers?

Answer 22

Adenylyl cyclase

Phospholipase C

Question 23

What is function of adenyl cyclase?

Answer 23

Activation of protein kinase. Catalyses synthesis of cAMP from ATP

Question 24

What is function of phospholipase C?

Answer 24

Involved in production of IPS3 and DAG

Question 25

What is gastric acid secretion stimulated by?

Answer 25

Histamine, acetylcholine and gastrin

Question 26

What group of receptors does H2 (histamine) belong to?

Answer 26

G protein-coupled receptors

Question 27

How does H2 affect cAMP?

Answer 27

1. Activation of H2 receptors in gut potentiates gastrin-induced acid secretion 2. Enhances cAMP 3. H2 receptor antagonist block H2 receptor --> inhibiting action of histamine 4. This reduces cAMP formation and acid secretion

Question 28

What are nuclear receptors?

Answer 28

Entirely intracellular - found in cytoplasm

Question 29

What must ligands of nuclear receptors be?

Answer 29

Lipophilic and hydrophobic

Question 30

What are primary targets of nuclear receptors?

Answer 30

Transcription factors as many molecules bind to proteins that act as regulators of mRNA synthesis

Question 31

How do nuclear receptors work?

Answer 31

1. Ligand binds to internal receptor 2. Change in shape is triggered, exposing DNA-binding site on receptor protein 3. Ligand-receptor complex moves into nucleus 4. Complex binds to specific regions of DNA and promotes production of mRNA from specific genes

Question 32

How are internal receptors unique?

Answer 32

Can directly influence gene expression without having to pass on signal to other receptors/messengers

Question 33

What are receptor kinases / enzyme-linked receptors?

Answer 33

High-affinity cell surface receptors for many growth factors, cytokines and hormones

Question 34

How do enzyme-linked receptors work?

Answer 34

Ligand binds to extracellular domain and signal is transferred through membrane, activating enzyme / activating cascades of intracellular signals

Question 35

What are most of these enzyme-linked receptors? What are they activated by? What do they cause?

Answer 35

Tyrosine-kinases, activated by growth factors, causing intracellular responses (insulin, growth factors)