L4 Receptors and signalling

Question 1

What are ligands?

Answer 1

Ligands are any molecules that bind to a receptor whether they are an agonist or an antagonist.

Question 2

Define endogenous agonists and can you give any examples?

Answer 2

They are chemical mediators that are found within the body that bind to a receptor producing a response.
E.g. acetylcholine, noradrenaline and insulin.

Question 3

Describe the general principle of chemical mediators

Answer 3

Chemical mediators are extracellular signal molecules that bind to specific receptors on target cells to initiate intracellular signals that alter cell behaviour through effector proteins, this is called cell signalling.

Question 4

What is signal transduction?

Answer 4

The process of converting extracellular signal to an intracellular signal or a second messenger is called signal transduction.

Question 5

What are the two ways that allows neurons to connect and communicate with each other?

Answer 5

Convergence and divergence

Question 6

How does convergence work?

Answer 6

Multiple neurons send signals to a single neuron, and the receiving neuron integrates these signals to produce a response

This allows for amplification of signaling

Question 7

What does divergence mean?

Answer 7

A single neuron sends signals to multiple neurons

This allows for coordinated responses involving multiple organs

Question 8

What are receptors?

Answer 8

Receptors are macromolecular proteins that serve as recognition sites for neurotransmitters, hormones etc

Question 9

What do receptors do?

Answer 9

They are proteins that can bind to a molecule, which then modulates some activity of the cell

Question 10

How many receptors are there roughly in the human genome?

Answer 10

1000s

Question 11

How are receptors classified and what are they?

Answer 11

Receptors are classified by their structure into 4 classes or superfamilies.
They are:
1. Type 1 - Ligand gated ion channels (ionotropic receptors)
2. Type 2 - G protein coupled receptors( metabotropic receptors)
3. Type 3 - Kinase linked receptors.
4. Nuclear - Intracellular receptors.

Question 12

What are the physiological features present in the first three classes of receptors?

Ligand-gated ion, G protein-coupled, Kinase- linked receptors

Answer 12

1. Each has transmembrane-spanning segments
2. Each possesses a ligand binding domain usually extracellular
3. Ligands are hydrophilic meaning they cannot cross the membrane.

Question 13

What are the structural differences with the nuclear receptor compared to the other receptors?

Answer 13

1. They contain polypeptides with multiple domains
2. Ligands are hydrophobic
3. Acts as transcription factors binding to DNA and regulating gene transcription
   E.g. Steroid hormone receptors including oestrogen receptors.

Question 14

Which chemical mediators use ligand-gated ion channels and G protein-coupled receptors?

Answer 14

Most small molecule chemical medaitors e.g. amino acid derived neurotransmitters

Question 15

Which chemical mediators use oestrogen receptors?

Answer 15

Steroidal hormones

Question 16

Which chemical mediators only use kinase-linked receptors?

Answer 16

Peptide hormones and cytokines

Question 17

Which chemical mediators only use G protein-coupled receptors?

Answer 17

Peptide hormones

Question 18

What is the time scale effects for ligand-gated ion channels, G protein coupled receptors, kinase - linked receptors and nuclear receptors?

Answer 18

Time Scale:
1. Ligand Gated ion channels - Milliseconds
2. G Protein-coupled receptors - Seconds
3. Kinase - linked receptors - Hours
4. Nuclear receptors - Hours.

Question 19

What is the order of an intracellular signal?

Answer 19

1. Ligand binding
2. Confrontational change in the receptor
3. Generation of an intracellular signal.

Question 20

What are the cellular effects of each receptor
activation? (4)

Answer 20

1. Electrical signals (Ligand gated ion receptor) Eg: triggering action potentials
2. Contractility and muscle movements (G protein coupled receptors).
3. Changes in enzyme activity (Kinase - linked receptors).
4. More channels to be inserted into the cell membrane. (Nuclear receptors).

Question 21

How are ligand gated ion channels opened?

Answer 21

Ligand gated ion channels are opened through agonists binding

Fast synaptic transmission (milliseconds).

Question 22

What are ACh, gluatemate and GABA all an example of?

Answer 22

Endogenous agonists

Question 23

What are the adaptations of ligand gated agonists?

Answer 23

1. They are composed of 3-5 subunits with transmembrane proteins.
2. They are complex arranged to form a central aqueous pore.

Question 24

Name and explain an excitatory ligand gated ion channel?

Answer 24

Nicotinic Acetylcholine Receptor = nAChR
1. They are present in the Neuromuscular junction and Autonomic nervous system
2. The agonists are ACh (Endogenous), Nicotine (Drug).

Question 25

What does the opening of nAChR do and explain the processes that follow?

Answer 25

Opening nAChRs results in excitation.
1. Ionotropic receptors are activated by excitatory receptors.
2. Ions flow through the open channels.
3. Membrane depolarisation - changes the potential of the cell.

Question 26

What are G protein coupled receptors formed from?

Answer 26

A single transmembrane protein

Receptor protein spans the membrane 7 times = 7 transmembrane domains

Question 27

What is the function of a G protein coupled receptor?

Answer 27

It’s to regulate effector proteins via a heterotrimeric GTP- binding protein (G protein)

Question 28

Explain the process of signal transduction by heterotrimeric G proteins.

Answer 28

1. Heterotrimeric G proteins undergo an enzymatical cycle.
2. Both α and βγ subunits can interact with effectors.

Question 29

Does the same G protein control the function of different effector proteins?

Answer 29

No - Different g proteins, different effectors.

Question 30

What can effectors be?

Answer 30

The may be:
1. Ion channels
2. Enzymes -
E.g. Adenylyl cyclase and phospholipase C , 2nd messengers are small diffusible molecules that spread the signal.

Question 31

Explain the amplification of signalling through GPCR regulated 2nd messenger cascades.

Answer 31

Transmitter activates receptor which activates G proteins. The activation of G proteins stimulates adenylyl cyclase to convert ATP to cAMP. cAMP activates protein kinase A which phoshorylates potassium channels.

Question 32

What is adenylyl cyclase?

Answer 32

It is an enzyme effector modulated by G proteins

Question 33

What are the two types of membrane- bound adenylyl Cyclases?

Answer 33

Gas- stimulated Adenylyl Cyclases
Gai - inhibited Adenylyl Cyclases

Question 34

How are intracellular Ca2+ levels increased?

Answer 34

They are increased by Gɑq through the enzyme phospholipase C.

Question 35

What effects do Gas (stimulatory) have on PKA?

Answer 35

Increases Adenylyl cyclase
Increases conc of cAMP
Increases Protein kinase A (PKA)

Question 36

What effects do Gai (inhibitory) have on PKA?

Answer 36

Decrease Adenylyl cyclase
Decreases conc of cAMP
Decreases Protein kinase A (PKA)