Lecture 2.1: Structure & Classification of Receptors

Question 1

Why is cell signalling important?

Answer 1

It permits effective communication and regulation of cells and cellular processes

Question 2

What are the steps in cell signalling?

Answer 2

Reception
Transduction
Response
Amplification

Question 3

Receptors are proteinaceous, what does this mean?

Answer 3

Capable of selectively binding a ligand (therefore, responses are selective as well)

Question 4

Receptor numbers are not static, what does this mean?

Answer 4

• Increased numbers of receptors =
  upregulation (increased sensitivity)
• Decreased numbers = downregulation
  (desensitisation or tachyphylaxis)
• Desensitisation occurs after a series of doses,
  tachyphylaxis may occur after the first dose

Question 5

What is a Ligand?

Answer 5

A molecule that binds to a receptor

Question 6

Examples of Ligands

Answer 6

• Hormones
• Neurotransmitters
• Growth Factors
• Drugs

Question 7

What is a ligand which binds and activates called?

Answer 7

Agonist

Question 8

What is Agonist Potency?

Answer 8

[Agonist] needed to produce 50% maximal response

Question 9

What is Agonist Efficacy?

Answer 9

Ability of an agonist, after binding, to activate receptors

Question 10

What is a ligand which binds and blocks agonist binding called?

Answer 10

Antagonist

Question 11

What is a which fails to produce maximal response on binding called?

Answer 11

Partial Agonist

Question 12

What type of receptor is a Ligand gated ion channels?

Answer 12

Ionotropic Receptors

Question 13

What type of receptor is a G protein-coupled receptors (GPCR)?

Answer 13

Metabotropic receptors

Question 14

What type of receptor is an Enzyme-linked receptors?

Answer 14

Kinase-linked receptors

Question 15

What type of receptor is an Intracellular receptors?

Answer 15

DNA-linked nuclear receptors

Question 16

What type of receptor is a nicotinic receptor?

Answer 16

Ionotropic receptor

Question 17

What us the structure of a nicotinic receptor?

Answer 17

• Formed from 5 subunits (2 a’s, 1
  beta, 1 gamma, 1 delta)
• There are 2 binding sites (on a’s)
  that need to be occupied before
  the receptor is activated

Question 18

What is the role of ionotropic glutamate receptors?

Answer 18

Mediates the effects of the excitatory amino neurotransmitter Glutamate

Question 19

What are the 3 Types of ionotropic glutamate receptors?

Answer 19

• NMDA
• AMPA
• Kainate

Question 20

How many subunits is the NMDA receptor made from?

Answer 20

7 subunits (monomers)

Question 21

How does the NMDA receptor work?

Answer 21

Highly permeable to Ca2+, and easily blocked by Mg2+ , receptor also requires glycine to bind

Question 22

What is the role of the NMDA receptor?

Answer 22

• Significant roles in synaptic plasticity (learning,
  memory also though pathophysiology e.g.
  chronic pain)
• Significant role in excitotoxicity caused by Ca2+
  overload

Question 23

Why are G-protein coupled receptors (GPCRs) called metabotropic receptors?

Answer 23

• Because they trigger chain of intracellular
  reactions known as the second messenger system
• The link to these second messengers are G-
  proteins hence the name!

Question 24

Examples of GPCRs (2)

Answer 24

• Adrenoreceptors (noradrenaline)
• Muscarinic receptors (acetylcholine)

Question 25

Why are GPCRs important in medicine?

Answer 25

They are important targets for drug action (c.50% of all modern drugs target GPCRs)

Question 26

What is the structure of enzyme linked receptors/kinase-linked receptors?

Answer 26

Have an extracellular ligand binding region and an intracellular catalytic domain (activated by binding) that is enzymatic in nature

Question 27

Why are enzyme linked receptors/kinase-linked receptors important in medicine?

Answer 27

Significant interest as drug targets to treat e.g. cancers and obesity

Question 28

Examples of enzyme linked receptors (4)

Answer 28

• Hormone (e.g. insulin)
  receptors
• Growth factor receptor
• Cytokine receptor
• Leptin receptor

Question 29

What is Autophosphorylation?

Answer 29

Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself.

Question 30

What are the target cells for insulins? (3)

Answer 30

• Hepatocytes
• Adipocytes
• Skeletal Muscle Cells

Question 31

What is the role of insulin?

Answer 31

An anabolic hormone, hypoglycaemic (reduces plasma glucose)

Question 32

What is the structure of the insulin receptor? How does insulin bind?

Answer 32

• Each receptor consists of a
  ligand binding region (a-
  subunit) which is linked via a
  disulphide bridge to the
  catalytic region (B- subunit)
• A disulphide bridge then
  links two of these monomers
  together producing a
  preformed dimer to which
  insulin binds
• Insulin then binds to
  extracellular a-subunit this
  results in
  autophosphorylation of the
  B-subunit
• SH2 domains of IRS (insulin
  receptor substrate) family
  proteins binds to the
  receptor

Question 33

How do Intracellular Receptors act on DNA? (3)

Answer 33

• Influence genetic expression of enzymes
• Influence genetic expression of cytokines
• Influence genetic expression of receptor proteins

Question 34

What drugs interact with intracellular receptors?

Answer 34

• Sex hormones
• Thyroid hormones
• Mineralocorticoids
• Vitamin D

Question 35

Steroid hormones pass through the cell
membrane with ease, though transporting
them to target sites is problematic, Why?

Answer 35

• The inactive receptor forms a complex with HSP90
• It blocks a region called the hinge site when hormone
  binds and HSP90 dissociates
• The hormone-receptor complex enters the nucleus
• Entry is facilitated by a nuclear localisation signal (NLS)
  that is located at the hinge site
• Generally, dimerisation occurs and the hormone-
  receptor complex interacts with DNA to influence gene
  expression