The Biochemical Basis for Therapy: Receptors and Signalling

Question 1

What are receptors?

Answer 1

The sensing elements of chemical communication

Question 2

What are receptors the targets of?

Answer 2

Neurotransmitters
Hormones
Other mediators
Many therapeutic agents

Question 3

What is autocrine signalling?

Answer 3

A cell signals to itself

Question 4

What is paracrine signalling?

Answer 4

A cell signals to its close neighbours

Question 5

What is endocrine signalling?

Answer 5

A cell signals via molecules transported by the blood to target distant cells

Question 6

What are the four types of receptors?

Answer 6

Ligand-gated ion channels
G protein-coupled receptors
Kinase-linked receptors
Nuclear receptors

Question 7

What are ligand-gated ion channels targeted by and what time scale is the action on?

Answer 7

Hydrophilic signalling molecules

Milisecond

Question 8

Where are ligand gated channels located?

Answer 8

Plasma membrane

Question 9

Where are G protein-coupled receptors located?

Answer 9

Plasma membrane

Question 10

What are G protein-coupled receptors targeted by and what time scale is the action on?

Answer 10

Hydrophobic signalling molecules

Second

Question 11

Where are kinase-linked receptors located?

Answer 11

Plasma membrane

Question 12

What are kinase-linked receptors mainly targeted by and what time scale is the action on?

Answer 12

Hydrophilic protein mediators

Hours

Question 13

What are nuclear receptors mainly targeted by and what time scale is the action on?

Answer 13

Hydrophobic signalling molecules

Hours/day

Question 14

Where are nuclear receptors located?

Answer 14

Intracellularly in the nucleus or cytoplasm

Question 15

What are ion channels?

Answer 15

Transmembrane pores formed by glycoproteins that span the membrane to create an ion conducting pathway for selected ions

Question 16

What are ion channels usually regulated by and what do they cause?

Answer 16

Signals that cause the channel to cycle reversibly between a closed state and open conformation

Question 17

What is the cycle ion channels go through between their closed state and open confirmation known as?

Answer 17

Gating

Question 18

What movement occurs when ion channels are open and what is the rate of movement?

Answer 18

Passive diffusion

Rapid

Question 19

What may ion channels be gated by?

Answer 19

Chemical signals
Transmembrane voltage
Physical stimuli

Question 20

What is a classic example of a ligand gated channel?

Answer 20

The nicotinic acetylcholine receptor of skeletal muscle and neurones

Question 21

What is the sequence of ligand-gated ion channel activation?

Answer 21

Agonist binds - conformation change
Channel opens - conduction pathway for selected ions
Ions flow down concentration gradient

Question 22

What movement does the nicotinic acetylcholine receptor allow?

Answer 22

Movement of Na+ into the cell and simultaneous movement of K+ out of the cell, causing membrane depolarisation and excitation

Question 23

What do most cell surface receptors signal via?

Answer 23

Second messenger systems

Question 24

What happens in second messenger systems?

Answer 24

Receptor activation modulates the activity of an effector that is generally an enzyme

Question 25

What are G protein-coupled receptors?

Answer 25

Receptors linked to a cell membrane located effector by intermediary G proteins

Question 26

What do enzyme effectors do?

Answer 26

Increase or decrease their rate of synthesis of second messenger molecules affecting the activity of targets within the cell

Question 27

What is the process of signal to a response via a G protein-coupled receptor?

Answer 27

``` Signal Receptor G protein Effectors activate an enzyme Second messenger Cellular targets Response ```

Question 28

What is the basic structure of a G protein-coupled receptor?

Answer 28

Integral membrane protein Single polypeptide with extracellular NH2 and intracellular COOH 7 transmembrane alpha-helical spans joined by 3 extracellular and 3 intracellular connecting loops

Question 29

What is the basic structure of a G protein?

Answer 29

Peripheral membrane protein 3 polypeptide subunits - alpha, beta and gamma Guanine nucleotide binding site in the alpha subunit that can hold guanosine triphosphate (GTP) or guanosine diphosphate (GDP)

Question 30

How are G proteins activated?

Answer 30

Agonist binding to the G protein-coupled receptor to which they preferentially coulple

Question 31

What occupies the inactive guanine nucleotide binding site of the alpha-subunit?

Answer 31

GDP

Question 32

What occupies the active guanine nucleotide binding site of the alpha-subunit and what does this cause?

Answer 32

GTP | The alpha and beta-gamma subunits dissociate from each other

Question 33

What occurs after the activation of a G protein-coupled receptor by an agonist?

Answer 33

Conformational change which is transmitted to the G protein alpha-subunit. This releases GDP and allows GTP to bind in its place The alpha-subunit separates from the receptor and beta-gamma-dimer. It generates a free GTP-bound alpha-subunit and beta-gamma-dimer, which are both signalling units.

Question 34

What is the guanine nucleotide exchange?

Answer 34

Where the alpha-subunit releases GDP and allows GTP to bind in its place

Question 35

What is subunit dissociation?

Answer 35

Where the alpha subunit separates from the receptor and beta-gamma-dimer

Question 36

After activation of a G protein-coupled receptor, what happens before the signal is switched off?

Answer 36

The G protein dissociates into separates alpha and beta-gamma subunits and the alpha subunit combines with and modifies the activity of the effector. The agonist may dissociate from the receptor but the signal can persist.

Question 37

How is a G protein-coupled receptor's signal switched off?

Answer 37

The alpha-subunit acts as an enzyme - a GTPase - to hydrolyse GTP to GDP and Pi and the signal is turned off. The G protein alpha subunit recombines with the beta-gamma subunit

Question 38

What does activation of a Gs or Gi protein by noradrenaline do?

Answer 38

Increases heart rate and force

Question 39

What does activation of a Gs or Gi protein by acetylcholine do?

Answer 39

Decreases heart rate and force

Question 40

What does activation of a Gg protein by noradrenaline do?

Answer 40

Causes vascular smooth muscle contraction

Question 41

What is an example of one form of signalling via receptor kinases?

Answer 41

The receptor for insulin

Question 42

What are nuclear receptors?

Answer 42

Ligand-gated transcription factors

Question 43

How do steroid hormones enter cells and what is this called?

Answer 43

Diffusion across the plasma membrane | Lipophilic

Question 44

What is the process of signalling via class 1 nuclear receptors?

Answer 44

Steroid hormones enter cells by diffusion across the membrane They combine with an intracellular receptor to produce dissociation of inhibitory HSP proteins The receptor steroid complex moves to the nucleus, forms a dimer and binds to hormone response elements in DNA The transcription of specific genes is switched on or off to alter mRNA levels and the rate of synthesis of mediator proteins