Intracellular Signalling (Receptor and Effector Mechanisms)

Question 1

What is signal transduction?

Answer 1

A basic process in molecular cell biology involving the conversion of a signal from outside the cell to a functional change within the cell.

Question 2

Where are receptors usually located?

Answer 2

The cell-surface, however some can be intracellular

Question 3

What are G protein-coupled receptors also known as?

Answer 3

Seven-transmembrane domain (7TM) receptors

Question 4

What is a ligand?

Answer 4

Ligand interact with receptors - ligand binding activates the receptor, which in turn directly or indirectly brings about a change in cellular activity

Question 5

What is an agonist?

Answer 5

Agonists bind to the receptor and activate it, leading to intracellular signal transduction events

Question 6

What is an antagonist?

Answer 6

They bind to the receptor but do not activate it, they block the effects of agonists at the receptor

Question 7

What is the difference between affinity and efficacy?

Answer 7

Affinity = how well it binds to the receptor
Efficacy = how well it causes the response

Question 8

What is the common basic structure of all GPCRs?

Answer 8

• Single polypeptide chain (300-1200 amino acids)
• 7 transmembrane spanning regions
• Extracellular N-terminal
• Intracellular C-terminal

Question 9

Which two regions of GPCRs can be responsible for ligand binding?

Answer 9

For some receptors the ligand binding site is formed by (2-3 of) the transmembrane domains

In other cases the N terminal region form the ligand binding site

Question 10

What happens when the ligand binds?

Answer 10

It changes the conformation of the transmembrane domains which turns the receptor ‘on’. Acivated GPCR facilitates GTP-GDP exchange on the alpha subunit of the G protein.

Question 11

What is a G protein?

Answer 11

Guanine-nucleotide binding protein - interacts with GPCR and made up of three subunits (heterotrimeric)

So G proteins able to bind with GTP, GDP etc

Question 12

What happens when the G protein interacts with the ‘on’ GPCR?

Answer 12

The alpha - beta/gamma complex immediately dissociates as they lose affinity for each other and then each interact with effector proteins

Question 13

What governs Receptor-G protein selection?

Answer 13

Activated GPCRs preferentially interact with specific types of G protein. The alpha subunit is a primary determinant.

In this way, an extracellular signal working via a specific GPCR will activative a single G protein and effectors in the cell to bring about a specific cellular response

Question 14

Which 2 subunits of the G protein are attached to the cell membane via lipid anchors?

Answer 14

Alpha subunit and Gamma subunit

Question 15

When the G protein is inactive does it bind GDP or GTP?

Answer 15

GDP (binds to alpha subunit)

Question 16

What initially happens when the ligand binds to the GPCR?

Answer 16

Conformational change

Question 17

Briefly describe the steps that follow a ligand binding to a GCPR

Answer 17

1) Ligand binds
2) GPCR undergoes conformational change
3) Alpha subunit exchanges GDP for GTP
4) Alpha subunit dissociates from beta/gamma
5) Subunits go on to regulate target proteins
6) GTP hydrolysed to GDP and subunits rejoin

Question 18

What are some examples of β2 adrenoceptor agonists?

Answer 18

Salbutamol, Salmeterol

Anti-asthma

Question 19

What are some examples of μ-opioid receptor agonists?

Answer 19

Morphine, Fentanyl

Analgesia/anaesthesia

Question 20

What are some examples of β adrenoceptor antagonists?

Answer 20

Propranolol, atenolol

Cardiovascular (hypertension)

Question 21

What are some examples of D2 dopamine receptor antagonists?

Answer 21

HALOPERIDOL, SULPIRIDE

neuroleptics (anti-schizophrenic)

Question 22

Is the N terminal of a GPCR extracellular or intracellular?

Answer 22

Extracellular

Question 23

Is the C terminal of a GPCR extracellular or intracellular?

Answer 23

Intracellular

Question 24

What does the alpha s subunit of a Gs protein do?

Answer 24

Stimulates adenylyl cyclase

Question 25

What does the alpha i subunit of a Gi protein do?

Answer 25

Inhibits adenylyl cylase

Question 26

What does adenylyl cyclase do?

Answer 26

Catalyses the reaction of ATP to cyclic AMP.

Cyclic AMP goes on to stimulate the production of protein kinase A

Question 27

What does protein kinase A do?

Answer 27

Goes on to phosphorylate other groups including enzymes that convert glycogen into glucose, enzymes that increase the rate of heart muscle contraction etc

Question 28

What does the alpha q subunit of a Gq do?

Answer 28

Stimulates phospholipase C

Question 29

What does phospholipase C do?

Answer 29

Stimulates the production of IP3 and DAG from PIP2

Question 30

What are the subunits of protein kinase A?

Answer 30

Catalytic units and regulatory units - cAMP binds to R units and C units dissociate to phosphorylate target proteins

Question 31

What are some examples of Gs coupled receptors?

Answer 31

β-adrenoceptors
D1 dopamine receptors
H2 histamine receptors

Question 32

What are some examples of Gi coupled receptors?

Answer 32

α2 adrenoceptors
D2 dopamine receptors
μ-opioid receptors

Question 33

What are some examples of Gq coupled receptors?

Answer 33

α1 adrenoceptors
M1 muscarinic receptors
H1 histamine receptors

Question 34

What happens when sympathetically released noradrenaline interacts with vascular smooth muscle α1 adrenoceptors?

Answer 34

Vasoconstriction

Question 35

How is bronchoconstriction caused?

Answer 35

Parasympathetically released acetylcholine can interact with bronchiolar smooth muscle M3 muscarinic receptors to cause bronchoconstriction

Question 36

Which pathway is activated when acetyl choline binds to M3 receptors on the smooth muscle membrane of the bronchi?

Answer 36

Phospholipase C pathway

Question 37

Which pathway is activated when noradrenaline binds to alpha1 receptors to cause vasoconstriction?

Answer 37

Phospholipase C pathway (GQ)

Question 38

What receptors on the heart increase heart rate?

Answer 38

Beta 1 receptors (GS)

Question 39

What receptors are responsible for bronchodilation?

Answer 39

Beta 2 receptors (GS)

Question 40

What does QISS QIQ mean?

Answer 40

Q - a1
I - a2
S - b1
S - b2

Q - m1
I - m2
Q - m3

QISS - sympathetic
QIQ - parasympathetic