Receptor-Effector Coupling

Question 1

What are 2 biological approaches to receptor classification?

Answer 1

1. Molecular structure

2. Signal transduction mechanism

Question 2

What 3 things affect the molecular structure of receptor proteins?

Answer 2

1. Amino acid sequence
2. 2ry and 3ry structure
3. Location of binding sites

Question 3

What 3 things affect the signal transduction mechanism?

Answer 3

1. Ion flux
2. Enzyme activity
3. Gene expression

Question 4

How many super families of receptors are there?

Answer 4

4

Question 5

Name the 4 receptor super families

Answer 5

1. Ligand-gated ion channels
2. G-protein-coupled receptors
3. Kinase-linked receptors
4. Nuclear receptors

Question 6

What is the major differences between families 1-3 and family 4?

Answer 6

First 3 families are on cell surface whereas nuclear receptors are intracellular

Question 7

What causes a group of receptors to become a superfamily?

Answer 7

Possess basic molecular and functional properties as each other but encoded by different genes which causes different shapes of receptors which respond to a specific mediator

Question 8

What 2 substances stimulate superfamily 1 receptors?

Answer 8

1. Acetylcholine

2. Nicotine (selectively)

Question 9

Name 2 competitive reversible antagonists to superfamily 1 receptors

Answer 9

1. Tubocurarine

2. Vecuronium

Question 10

Name a non-competitive antagonist to superfamily 1 receptors

Answer 10

Lidocaine

Question 11

What is the function of neuromuscular blocking agents such as tubocurarine?

Answer 11

Prevent skeletal muscle contraction during surgery

Question 12

How does lidocaine act as a non-competitive antagonist to superfamily 1 receptors?

Answer 12

Antagonises the action of acetylcholine at some point in the chain

Question 13

What are 3 characteristics of nicotinic cholinoceptors in neuromuscular junctions?

Answer 13

• Receptor is made up of 5 sub-units
• Primary amino acid sequence runs from N terminal to C terminal
• 4 transmembrane helices allow sub-unit to move through membrane and be anchored
• 2nd helix of each sub-unit comprise the channel pore

Question 14

How is a nicotinic receptor activated?

Answer 14

A molecule of acetylcholine must bind to both a sub-units in the receptor

Question 15

What are 3 characteristics of receptors in superfamily 2?

Answer 15

• Single protein spans 7 times across membrane to anchor it
• Extracellular N terminal binds to substances
• Cytoplasmic and extracellular loops found between different parts of protein spanning membrane

Question 16

What are receptors in superfamily 2 coupled with?

Answer 16

Heterotrimeric G-proteins

Question 17

What are 3 characteristics of a G-protein?

Answer 17

1. Consist of 3 sub-units (alpha, beta, gamma)
2. Molecular switches
3. Communicate between superfamily 2 receptor and an effector

Question 18

What 3 sites are found on the a sub-unit of a G-protein?

Answer 18

1. Receptor interaction site
2. GTP binding site
3. Target protein interaction site

Question 19

Describe the switching on and off of G-proteins

Answer 19

• GTP binds to the a subunit which turns on G-protein
• Intrinsic enzyme activity of GTPase breaks down GTP bound to sub-unit
• GTP broken down to GDP which is released from a sub-unit as the reaction stops

Question 20

What is a second messenger?

Answer 20

Intracellular chemical, the concentration of which can be altered rapidly and reversibly on activation of a cell surface receptor, to regulate activity of an internal effector to produce intracellular response

Question 21

What are the 2 mechanisms which second messengers generally come about?

Answer 21

1. G-protein activates ion channel which allows ion to accumulate
2. G-protein activates enzymes which generate ions

Question 22

What can regulate concentration of ions acting as second messengers?

Answer 22

Internal effector

Question 23

What gives G-proteins specificity?

Answer 23

Different a sub-units are encoded by a different gene or splice variants

Question 24

How can G-proteins be stimulator or inhibitory?

Answer 24

Can induce a conformational change in effector protein to more or less active states

Question 25

Give 3 examples of effectors regulated by G-proteins

Answer 25

1. Adenylate cyclase 2. Phospholipase C-b 3. Voltage-gated calcium/potassium channels

Question 26

Describe cyclic AMP signalling pathway

Answer 26

- Noradrenaline or adrenaline activates G-protein - Enhanced binding of GTP activates G-protein - Interaction with adenylate cyclase which catalyses production of second messenger - Second messenger regulates cAMP-dependent protein kinase - Kinase catalyses protein phosphorylation to bring about cellular response

Question 27

Name 2 types of drugs and their function which target cyclic AMP signalling pathway

Answer 27

1. β₁ adrenoceptors - Enhance cardiac muscle action | 2. β₂ adrenoceptors - Bronchodilation

Question 28

What is an example of a β₁ adrenoceptor drug?

Answer 28

Dobutamine

Question 29

What is an example of a β₂ adrenoceptor drug?

Answer 29

Salbutamol

Question 30

Name an antagonist drug of β₁ adrenoceptors

Answer 30

Beta blockers e.g. atenolol

Question 31

What are 3 ways a cyclic AMP signalling pathway can be terminated?

Answer 31

1. Breaking down the mediator 2. Breaking down GTP 3. Metabolism for cAMP in cytoplasm

Question 32

How is cAMP metabolised in cytoplasm?

Answer 32

Enzyme cyclic AMP phosphodiesterase hydrolyses across ring leading to linear molecules which does not activate kinase

Question 33

How does caffeine lead to a greater response of cyclic AMP signalling pathway?

Answer 33

Inhibits the action of cAMP phosphodiesterase

Question 34

What are 2 types of superfamily 3 receptors?

Answer 34

1. Receptors directly linked to tyrosine kinase | 2. Receptors directly linked to guanylate cyclase

Question 35

Name 4 receptors which are directly linked to tyrosine kinase

Answer 35

1. Insulin 2. Insulin-like growth factor 3. Epidermal growth factor 4. Cytokine

Question 36

Name 2 receptors which are directly linked to guanylate cyclase

Answer 36

1. Natriuretic peptide | 2. Guanylin

Question 37

What is the function of tyrosine kinase?

Answer 37

Phosphorylates tyrosine amino acids into proteins

Question 38

What is the function of guanylate cyclase?

Answer 38

Creates cyclic GNP

Question 39

Describe the 5 steps of activation and transduction of tyrosine kinase-linked receptors?

Answer 39

- Ligand binds to receptor which causes conformational change in receptor - Dimer forms - Dimer formation increases enzyme activity - Enzyme phosphorylates tyrosine groups on adjacent molecule in the dimer - Dimer splits

Question 40

What is the function of SH-2 domain protein?

Answer 40

Recognize the phosphorylated amino acids in which phosphorylation helps binding of proteins to enzymes

Question 41

Give an example of a drug which targets tyrosine kinase-linked receptors

Answer 41

Herceptin

Question 42

How does herceptin slow tumour progress

Answer 42

Bind to proteins which prevents receptors from binding with growth factors and slowing tumour progress

Question 43

Name 3 types of receptors in uperfamily 4

Answer 43

1. Receptors for lipophilic steroid hormones 2. Receptors for lipid mediator present in cells 3. Receptors for lipophilic vitamins

Question 44

Describe the mechanism of action of superfamily 4 receptors

Answer 44

- Agonist binds to intracellular receptors - Zinc finger domain opens and binds to hormone responsive elements - Activity of RNA polymerase, gene transcription and translation of mRNA is affected - This allows synthesis of new proteins and altered cellular reponse

Question 45

Name 2 type of nuclear receptor therapeutics

Answer 45

1. Aldosterone receptor antagonists e.g. spironolactone | 2. Corticosteroid receptor agonists e.g. budesonide