Signal transduction

Question 1

What is transduction?

Answer 1

This is a process of ligand binding which generates a cellular response via other intracellular signalling components.

Question 2

What receptor type are ~40% of prescription drugs targeted at?

Answer 2

GPCRs

Question 3

Name two B adrenoceptor agonists

Answer 3

Salbutamol and salmetrol

Question 4

To what receptor can some analgesia drugs be targeted?

Answer 4

u-opioid receptor agonists including morphing and fentanyl

Question 5

What is the action of propranolol and atenolol?

Answer 5

These are B receptor antagonists. E.g. Reduce sympathetic activity in the heart.

Question 6

What is the common basic structure of a GPCR?

Answer 6

7 transmembrane domains, with an extracellular N terminal and intracellular C terminal.

Question 7

Where are non-activated G proteins found in a cell?

Answer 7

These move around on the plasma membrane and when a receptor is activated they are attracted to it.

Question 8

What happens when the activated GPCR interacts with the G protein?

Answer 8

GDP on the a subunit is exchanged for GTP and so the complex dissociates into two separate parts.

Question 9

How long can G protein activation last for?

Answer 9

It lasts indefinitely and continues until the GTP is hydrolysed back to GDP and the two subunits reform the inactive complex.

Question 10

How many different types of G protein are there?

Answer 10

G proteins show great diversity because the human genome encodes for many different types of subunits which can all combine differently.

Question 11

Why can the same signalling molecule have different effects depending on the receptor?

Answer 11

There are many different types of G protein and it is possible for them to cause the opposite response by having the opposite effect on the same effector molecule.

Question 12

What is the significance of the cholera toxin interfering with the GTPase stage of a G protein?

Answer 12

This means that GTP is never hydrolysed and so once activated the protein signals for hours driving up AMP concentrations which causes water channels to open and water to move into lumen –> diarrhoea.

Question 13

What is the function of the pertussis toxin?

Answer 13

This binds to Ga proteins and prevents GDP to GTP exchange meaning that the protein cannot become activated and so ligand binding does not link to a cellular response.

Question 14

What are the two effectors that G proteins can act on?

Answer 14

Ion channels and enzymes.

Question 15

What does adenylyl cyclase do?

Answer 15

It catalyses the conversion of ATP to cAMP.

Question 16

State the effects of Gas and Gai on adenylyl cyclase.

Answer 16

Gas is stimulators whilst Gai is inhibitory.

Question 17

What does cAMP in a cell act upon?

Answer 17

Cyclic AMP dependant protein kinase, Epacs (guanine nucleotide exchange factors) and cyclic-nucleotide gated ion channels (CNGs)

Question 18

How does cAMP act on protein kinase?

Answer 18

It binds at the regulatory subunit, and the catalytic subunits dissociate and phosphorylate target proteins.

Question 19

What catalyses PIP2 –> IP3?

Answer 19

Phospholipase C

Question 20

Which G protein activates Phospholipase C?

Answer 20

Gaq

Question 21

What is the function of IP3 in cells?

Answer 21

It binds to receptors on calcium channels, allowing calcium release from the Endoplasmic recticulum.

Question 22

What is signal amplification?

Answer 22

This occurs in cells and means that a massive cellular response can be reduced from a relatively small number of Extracellular signalling molecules binding to the cell surface.

Question 23

Describe the link between sympathetic adrenaline and increased inotropy in the heart.

Answer 23

Adrenaline binds to B1 receptors in the heart and this activates Gas which causes activation of adenylyl cyclase and conversion of ATP to cAMP which activates cAMP dependant protein kinase. This phosphorylates VOCC channels allowing more calcium to enter the cell, more CICR and therefore increased contractility.

Question 24

Describe how GPCR activation in smooth muscle cells causes vasoconstriction.

Answer 24

Gaq proteins catalyse PIP2 –> IP3 and this binds to receptors on the endoplasmic recticulum leading to calcium release, greater contraction and therefore vasoconstriction.

Question 25

What is the parasympathetic effect on the lungs?

Answer 25

M3 receptors are Gaq and so when ACh binds this activates Phospholipase C leading to IP3 production. This binds to receptors on the ER leading to increased intracellular calcium and therefore bronchoconstriction.

Question 26

How is neurotransmitter release modulated in the CNS/PNS?

Answer 26

GPCRs on the presynaptic cell activates G proteins. For example, GBY subunit dissociates and inhibits some of the VOCC channels and so prevents calcium influx and therefore neurotransmitter release. This occurs when there are already high concentrations of neurotransmitter in the synaptic cleft.

Question 27

What does activation of M2 receptors at the SA node cause?

Answer 27

This is a parasympathetic response and leads to increased open probability of K+ channels. This causes hyperpolarisation of the membrane which has a negative chronotrophic effect as it takes longer for an action potential to be fired.