Receptors and Signalling

Question 1

What is a ligand?

Answer 1

Any molecule that binds to a receptor
May be an agonist or antagonist

Question 2

What are endogenous agonists?

Answer 2

Chemical mediators that are found naturally in the body that bind to a receptor producing a response
e.g. ACh, noradrenaline, insulin

Question 3

What are nonendogenous agonists?

Answer 3

Drugs

Question 4

What is convergent signalling?

Answer 4

Single cells can integrate information and create a single response
- All cells express multiple types of receptors

Question 5

What is amplification of signalling?

Answer 5

Different types of receptors may use similar transduction mechanisms

Question 6

What is divergent signalling?

Answer 6

Allows coordinated responses involving multiple organs
- Most EC signal molecules can act on more than one type of cell

Question 7

What are receptors?

Answer 7

Macromolecular proteins that serve as recognition sites for chemicals and used in cell-cell communication
Also any protein of a cell that can bind a molecule, to modulate an activity of the cell

Question 8

How are receptors classified?

Answer 8

• Receptors within a class share common overall features
• There are three classes on cell surface each with:
  - Transmembrane-spanning segments
  - Ligand-binding domain (extracellular)

Question 9

What are the 4 receptor types?

Answer 9

Type 1 - Ligand-gated ion channels (ionotropic receptors)
Type 2 - G protein coupled receptors (metabotropic) - can influence metabolic cascade within cell
Type 3 - Kinase-linked receptors e.g. insulin receptors
Type 4 - Nuclear receptors (no transmembrane proteins)

Question 10

What are nuclear receptors?

Answer 10

• Polypeptides with multiple domains
• Ligands hydrophobic so can cross membrane
• Act as transcription factors - binding to DNA and regulating gene expression
  e.g. steroid hormone receptors

Question 11

What receptor types do small molecule chemical mediators use?

Answer 11

Type 1 and 2

Question 12

What receptor types do peptide hormones use?

Answer 12

Type 2 and 3

Question 13

What receptor types do steroidal hormones use?

Answer 13

Type 4

Question 14

How are signals transduced?

Answer 14

1) Ligand binding
2) Conformational change in receptor
3) Generation of intracellular signal or second messenger

Question 15

What does transduction mechanism and type of IC signal influence?

Answer 15

Type, speed, duration of response

Question 16

When do ligand-gated ion channels open?

Answer 16

On agonist binding
Involved in fast synaptic transmission
The endogenous agonists are fast/classical NTs stored in synaptic vesicles e.g. ACh, Glutamate, GABA

Question 17

How are ligand-gated ion channels structured?

Answer 17

• Composed of 3-5 subunits (i.e. transmembrane proteins)
• Complex arrangement to form central aqueous pore , usually ligand binding domain on outisde

Question 18

When do ligand-gated ion channels close?

Answer 18

When agonist is removed or receptor enter ‘desensitised state’ - takes time for it to be ready to open again

Question 19

What are nAChRs?

Answer 19

Nicotinic acetylcholine receptors
- An excitatory ligand gated ion channel
- Pentameric and heteromeric - 5 different subunits make up channel

Question 20

Where are nAChRs found?

Answer 20

Neuromuscular junctions
Autonomic nervous system
Some parts of brain

Question 21

What are the agonists of nAChRs?

Answer 21

Endogenous - ACh
Non-endogenous - Nicotine

Question 22

What does opening nAChRs cause?

Answer 22

Results in excitation
1) Excitatory NTs (ACh) bind to nAChR activating them
2) Ions (Na+) flow through open channels
3) Changes the potential of the cell - membrane depolarisation

Question 23

How is inhibition caused via LG ion channels?

Answer 23

GABA activates GABA(A) receptors which allow Cl- through
Causes membrane hyperpolarisation

Question 24

What is the structure of G protein coupled receptors?

Answer 24

Single transmembrane protein
7 transmembrane domains
EC binding domain on outside
G protein binding domain on inside

Question 25

What is the role of GPCRs?

Answer 25

Regulate effector proteins via a heterotrimeric GTP-binding protein (G protein)

Question 26

What do G proteins bind?

Answer 26

Guanasine molecules

Question 27

How are G proteins structured?

Answer 27

alpha subunit (GDP bound)
beta subunit
gamma subunit
Both alpha, and beta-gamma subunits can interact with effectors

Question 28

What is the process of signal transduction by G proteins?

Answer 28

1) G protein comes across receptor with NT bound - changes configuration of a-subunit
2) GTP molecule binds instead of GDP - activates G protein
3) a-GTP and By subunits dissociate from each other and from GPCR
4) a and By subunits can target and activate other molecules
5) GTP catalysed and loses phosphate to become GDP
6) Subunits come back together again

Question 29

How many G proteins can be activated at one time?

Answer 29

One receptor can activate 10-20 G proteins

Question 30

What are the effectors that G protein subunits act on?

Answer 30

Ion channels
Enzymes e.g. adenylyl cyclase, phospholipase C - go on to activate 2nd messengers (amplification of signalling through these cascades)