S1: Receptor Mechanism I

Question 1

What does a indigenous neurotransmitter/hormone do?

Answer 1

It occupies a receptor (affinity) and causes a response (efficacy) like a lock and key

Question 2

What does an exogenous agonist do?

Answer 2

It will be different in shape slightly but will mimic the indogenous response

Question 3

What are the properties of receptors?

Answer 3

• tissue selectivity
• chemical selectivity
• extracellular/intracellular communication
• amplification

Question 4

Name the 4 different type of receptors

Answer 4

Receptors
Enzyme
Carrier molecules
Ion channels

Question 5

What are receptors locates in plasma membrane of cells called?

Answer 5

Transmembrane proteins

Question 6

How do transmembrane proteins communicate information to cells?

Answer 6

They are different receptor groups that bind drugs at external sites to communicate distinct types of information to the cell

Question 7

What are the 4 classifications of receptor families?

Answer 7

Ligand gated receptors
G protein-coupled receptors
Tyrosine kinase receptors
Intracellular receptors

Question 8

How many protein subunits are ligand gated receptors made of?

Answer 8

5

Question 9

How many transmembrane regions (membrane spanning protein domain) does one protein subunit in a ligand gated receptor have?

Answer 9

4

Question 10

How many transmembrane regions are ligand gated receptors made of?

Answer 10

20

Question 11

What is the extra cellular site where a ligand binds to in a ligand gated receptor called?

Answer 11

N- terminal region

Question 12

Explain the signal transduction mechanism of ligand gated receptors

Answer 12

1. Ligand binds to receptor
2. Conformational change in subunits
3. Ion channel opens
4. Increase in ion flux
5. Change in cell excitability- more positive inside the cell causing depolarisation

Question 13

What is conformation change?

Answer 13

A change in shape of a macromolecule

Question 14

Examples of Ligand gated receptor

Answer 14

Nicotinic: controlling skeletal muscle contraction
Glutamate: controlling AP firing in brain

Question 15

How many proteins is G protein coupled receptors made of?

Answer 15

1 protein

Question 16

How many transmembrane regions does G protein coupled receptors have?

Answer 16

7 transmembrane regions (1 protein spans the membrane 7 times)

Question 17

What is the ligand binding site on G protein coupled receptors called?

Answer 17

N terminal

Question 18

What is the C terminal on G protein coupled receptors?

Answer 18

G protein binding region

Question 19

Explain the signal transduction mechanism of G protein coupled receptors

Answer 19

1. Ligand binds to receptor
2. Conformational change in receptor
3. Activation of G proteins
4. Production of intracellular messengers
5. Cellular function

Question 20

Compare the speed of G protein coupled receptors to ligand gated receptors

Answer 20

G proteins are slower taking second to minutes due to the fact that messengers need to be produced

Ligand gated receptors are very fast responses that occur on the millisecond (ms) timescale.

Question 21

Explain how G protein work when drug binds to receptor

Answer 21

1. When no drug is bound, G protein is bound to receptor. GDP is bound to the a subunit at rest.
2. The drug binds
3. Change in receptor conformation
4. Now GTP is bound to Ga subunit - this is because GTP has much higher affinity to the new shape of receptor so removes GDP
5. Ga subunit dissociates from receptor and induces a cellular response
6. Intrinsic Ga subunit GTPase activity- GTP dephosphorylates to GDP
7. G-protein a B y subunits reassociate and bind with unbound receptor

Question 22

What do the B and y subunits in G protein do?

Answer 22

They tether the G protein to receptor and to the membrane

Question 23

What does the a subunit in G protein do?

Answer 23

It detaches and goes off and activates the mechanism that leads to intracellular messengers

Question 24

What does the a subunit in G protein do?

Answer 24

It detaches and goes off and activates the mechanism that leads to the production of intracellular messengers

Question 25

Give three examples of the type of a subunit

Answer 25

The type of a subunit determine which systems inside cell are activated Gas (stimulatory) Gai (inhibitory) Gaq Different a subunits interact with specific targets

Question 26

Explain the GaS mediated pathway

Answer 26

Gas stimulates adenylate cyclase (AC) and converts ATP into cyclic AMP (cAMP). This increases cAMP levels which stimulates protein kinase A (PKA)

Question 27

Explain the Gai mediated pathway

Answer 27

Gai inhibits adenylate cyclase (AC) and uses ATP to decrease cyclic AMP (cAMP) levels. This inhibits protein kinase A (PKA)

Question 28

Explain the Gaq mediated pathway

Answer 28

Gaq binds to phospholipase C (PLC) which converts PIP2 into IP3 and DAG. - IP3 binds to IP3 receptors on the SR membrane which opens a calcium channel that increases concentration of cytosolic calcium levels - DAG activates protein kinase C (PKC) This can increase the permeability of ion channels

Question 29

Activation of G protein couples receptors regulate many biological processes Give examples

Answer 29

Enzyme, transporters Contractile proteins Gene expression Ion channels

Question 30

Explain the structure of a tyrosine kinase receptor

Answer 30

- Monomer - 1 single protein subunit - 1 transmembrane domain - N terminal is extracellular: Bind ligand - C terminal is intracellular: Binds effector

Question 31

Where are tyrosine kinase receptors found?

Answer 31

Areas of growth factors, cytokines, hormones

Question 32

Explain the signal transduction mechanism of tyrosine kinase receptors

Answer 32

1. Ligand binding to monomers induces dimerisation 2. Monomers phosphorylate tyrosine residue in each another 3. Phosphorylated intracellular domains bind enzymes/other cellular proteins 4. Cellular function

Question 33

What is the speed of response of tyrosine kinase?

Answer 33

Slow response that can take minutes, hours, days

Question 34

Give an example of a tyrosine kinase receptor

Answer 34

Insulin receptor

Question 35

Where are intracellular (nuclear) receptors found?

Answer 35

Within the cytoplasm of the cell

Question 36

What is the structure of intracellular (nuclear) receptors?

Answer 36

Monomer - 1 single protein subunit - DNA binding side - N terminal: binds heat shock protein (HSP) and agonist - C terminal: Controls transcription

Question 37

What is the main function of intracellular (nuclear) receptors?

Answer 37

Regulates gene transcription

Question 38

Explain the signal transduction mechanism of intracellular (nuclear) receptors

Answer 38

1. Drug crosses the plasma membrane (lipophilic) 2. Hormone (drug) displaces HSP and therefore binds to N-terminal 3. Hormone/receptor complex enters nucleus and binds to hormone responsive element on a gene DNA binding site 4. Modulation of gene transcription

Question 39

What is the speed of intracellular (nuclear) receptors?

Answer 39

Slow response | Hours, days, months and beyond

Question 40

Glucocorticoids are very important anti inflammatory drugs (hormone) What is the cellular mechanism of glucocorticoids?

Answer 40

- Glucocorticoid get inside cell and binds to receptor (GCR) and dissociates HSP - Glucocorticoid/GCR complex is translocated to the nucleus - Expression of genes can be increased or decreased (e.g. processes involved in inflammation are down regulated)

Question 41

Name the excitatory muscuranic receptors

Answer 41

M1 M3 M5 They take the Gaq pathway where they activate Phospholipase C

Question 42

Name the inhibitory muscuranic receptors

Answer 42

M2 M4 | They take the Gai pathway where they inhibit adenylate cyclase