11. Biological Signalling And Receptors

Question 1

What are the 2 ways of intercellular signalling?

Answer 1

Signalling by secreted molecules

Signalling by plasma membrane-bound molecules

Question 2

What are the 3 subdivisions of signalling molecules?

Answer 2

Local chemical mediators (paracrine)
Hormones (endocrine)
Neurotransmitters (synaptic)

Question 3

What is a receptor?

Answer 3

Molecule that recognises specifically a second molecule (ligand) or family of molecules and which in response to land binding brings about regulation of a cellular process
In unbound state a receptor is functionally silent

Question 4

What is a ligand?

Answer 4

Any molecule that binds specifically to a receptor site

Question 5

What is an agonist?

Answer 5

A ligand which when it binds can produce activation of a receptor

Question 6

What is an antagonist?

Answer 6

A ligand that combines with a receptor site and does not cause activation, it opposes the actions of an agonist
Acts as a competitive inhibitor

Question 7

What is the role of receptors in cellular physiology?

Answer 7

Signalling by hormones/local chemical mediators
Neurotransmission
Cellular delivery
Control of gene expression
Cell adhesion
Modulation of immune response
Sorting of intracellular proteins
Release of intracellular calcium stores

Question 8

Binding affinity at receptor binding sites

Answer 8

Affinity of ligand binding at receptor sites is generally much higher than binding of substrates and allosteric regulators to enzyme sites

Question 9

How are receptors classified?

Answer 9

Specific physiological signalling molecule (agonist) recognised
E.g. adrenaline receptors

Question 10

How are receptors sub-classified?

Answer 10

Affinity (tightness of binding) of a series of antagonists

Question 11

What are the 2 receptor types of acetylcholine receptors?

Answer 11

Nicotinic

Muscarinic

Question 12

Difference between acceptor and receptor?

Answer 12

Receptor: silent at test, agonist binding stimulates a biological response
Acceptor: operate in absence of ligand, ligand binding alone produces no response

Question 13

What are the 4 types of signal transduction?

Answer 13

1. Membrane-bound receptors with integral ion channels (fastest)
2. Membrane-bound receptors with integral enzyme activity
3. Membrane-bound receptors which couple to effectors through transducing proteins (most common)
4. Intracellular receptors

Question 14

Classic receptor family examples

Answer 14

Nicotinic acetylcholine receptor
GABA receptor
Glycine receptor

Question 15

Non-classical ligand-gated ion channels examples

Answer 15

ATP sensitive potassium channel

Ryanodine receptor

Question 16

Examples of membrane-bound receptors with integral enzyme activity

Answer 16

Atrial natriuretic peptide receptor (GTP-> cGMP)

Growth factor receptors - insulin, epidermal growth factor

Question 17

Signalling via tyrosine kinase-linked receptors

Answer 17

Tyrosine residues (receptor) are intracellular
An agonist (insulin) binds to receptor
Tyrosine kinase activated and phosphorylates chain its connected to (receptor)
Causes conformational change
Autophosphorylation then takes place
One route: allows proteins that have phosphotyrosine recognition site in them to come along and bind to receptor, enzyme then active
Second route: receptor is phosphorylated, transducer binds, transducer then phosphorylated, enzyme then binds to transducer and is activated

Question 18

Membrane-bound receptors that signal through transducing proteins
(Seven transmembrane domain receptors)

Answer 18

Coupled through GTP-binding regulatory proteins (G-proteins) to enzymes or channels
Adrenaline binding to beta-adrenoceptors activates enzyme adenylyl cyclase via a G-protein (Gs)
Acetylcholine binding to M2 muscarinic acetylcholine receptors stimulates potassium channel opening via a different G-protein (Gi)

Question 19

Examples of G-protein coupled receptors

Answer 19

Bacteriorhodopsin

Beta-2-adrenoceptor

Question 20

Cellular activation and inhibition

Answer 20

Responses to receptor activation can lead to cellular activation or inhibition depending on the receptor activated

Question 21

Cardiac pacemaker cells activation and inhibition

Answer 21

Activation: noradrenaline -> beta-1-adrenoceptors -> increased heart rate
Inhibition: acetylcholine -> M2 muscarinic receptors -> slowing of heart rate

Question 22

Hepatocytes activation and inhibition

Answer 22

Activation: insulin -> stimulates glycogen synthesis from glucose
Inhibition: glucagon -> stimulates glycogen breakdown to glucose