Intracellular Signalling

Question 1

Describe paracrine signalling

Answer 1

Local, uses chemical mediators

Question 2

Describe endocrine signalling

Answer 2

Utilises the blood stream, uses hormones

Question 3

Describe synaptic signalling

Answer 3

Uses neurotransmitters, between a neuron and either another neuron or effector tissue

Question 4

Describe a receptor

Answer 4

A molecule which specifically recognises a ligand or family of, and in response to this binding brings regulation of a cellular process.
In its unbound state, receptors are functionally silent.

Question 5

Describe a ligand.

Answer 5

Any molecule that binds specifically to a receptor site.

Question 6

What is the difference between an agonist and antagonist?

Answer 6

An agonist activates a receptor

An antagonist binds without causing a response.

Question 7

Describe the difference between the affinity of a ligand at receptor sites, and the affinity of a substrate to an enzyme site.

Answer 7

The affinity of a ligand is generally much higher.

Question 8

How are receptors classified?

Answer 8

Primarily by specific signalling molecules, then sub-classified by their affinity for a specific series of antagonists.

Question 9

What are the four methods of signal transduction?

Answer 9

Receptor with integral ion channel
Receptor with integral enzyme
Receptor coupled to effectors through transducing enzymes
Intracellular receptor with DNA binding site

Question 10

Decribe the difference between a receptor and acceptor

Answer 10

Receptors are silent at rest and stimulate biological responses with ligand binding.
Acceptors operate in the absence of a ligand, binding alone has no response.

Question 11

Describe the methotrexate receptor

Answer 11

Modulated by methotrexate.
Is the enzyme dihydrofolate reductase.
Is an acceptor

Question 12

Describe the nicotinic acetylcholine receptor

Answer 12

Causes depolarisation on ligand binding
Is an integral ion channel
Permeable to sodium, potassium and calcium.
Pentameric with two alpha subunits that ACh binds to.
The change in conformation on binding increases the negative charge in the channel, allowing selectivity for ions.
Multiple transmembrane domains.

Question 13

Describe the GABA recepor

Answer 13

Integral ion channel
Amino acid gated
Causes hyperpolarisation
Permeable to chloride ions

Question 14

Describe the implication of glutamate receptors in brain damage.

Answer 14

Integral ion channel

Glutamate is released in the brain when it is damaged, causing calcium influx into the cells which is toxic.

Question 15

Describe the ATP-sensitive potassium channel.

Answer 15

A non-classical integral ion channel
Closes on intracellular ligand binding
Found in beta cells of the pancreas.

Question 16

Describe a ryanodine receptor

Answer 16

Is actually an acceptor.
Causes muscle block and activation by increasing calcium release from the ER.
Calcium is also a ligand.

Question 17

Describe the general structure of a receptor with integral enzyme activity.

Answer 17

One transmembrane domain with a binding domain extracellularly and a catalytic domain intracellularly.
Have a partner subunit.

Question 18

Describe growth factor receptors

Answer 18

Linked to tyrosine kinase which allows autophosphorylation
Then an enzyme can bind and take the receptor into the cell, or it binds to a transducer protein which then phosphorylates the start point for an enzyme cascade.

Question 19

Describe the insulin receptor.

Answer 19

Two alpha subunits extracellularly at the N-terminus which contains the insulin binding domain. This is attached to a beta subunit, which is bonded to the transmembrane domain.
The tyrosine kinase domain within the cell is near the C terminus.

Question 20

What does G-protein stand for?

Answer 20

GTP-binding regulatory protein

Question 21

Describe the use of GPCR in the heart (briefly) by the sympathetic and autonomic nervous systems.

Answer 21

Sympathetic - adrenaline or noradrenaline binds to beta-adrenoceptors. Gs activates adenylyl cyclase which increases cAMP production.

Parasympathetic - ACh binding to M2 uses Gi to inhibit adenylyl cyclase, decreasing cAMP production. The beta-gamma subunit stimulates potassium channel opening.

Question 22

Where is the binding domain in a GPCR?

Answer 22

In the bilayer as a cleft formed by the transmembrane domain

Question 23

What terminus is the G-protein coupling domain nearest?

Answer 23

C

Question 24

Describe activation of an intracellular receptor.

Answer 24

A large inhibitory protein complex is bound at rest.
On binding of a ligand a conformational change occurs which releases this to reveal the DNA binding domain (zinc fingers)