Biological Signalling and Receptors - Drug Targets

Question 1

Give examples of intercellular signalling.

Answer 1

Paracrine where a local mediator (signalling molecule) is released via exocytosis from one cell and then transported around in the tissue to another cell.
Signalling by plasma membrane-bound molecules where the signalling molecule is stuck on the plasma membrane of one cell and interact with a receptor on the other cell.
Endocrine where a signalling molecule called a hormone is released in the blood stream and work on a distant tissue.
Synaptic where a neurotransmitter (signalling molecule) is released into the synaptic cleft to bind to a receptor to elicit a response. Usually an action potential.

Question 2

What’s the difference between a cell-surface and intracellular receptor?

Answer 2

The signalling molecule interacts with the receptor on the plasma membrane in one case.
An intracellular receptor is inside the cell, usually on the nuclear membrane or the ER membrane. Steroid for example which are small hydrophobic molecules can diffuse via the plasma membrane and into the cell.

Question 3

Define receptor.

Answer 3

A receptor is a molecule that recognises specifically a second molecule (ligand) or family of molecules which in response to ligand binding brings about regulation of a cellular process.

Question 4

Define ligand.

Answer 4

A ligand is any molecule that binds specifically to a receptor site.

Question 5

What are the purposes of a ligand?

Answer 5

To either activate or inhibit a receptor in order to create a response or inhibit that response.

Question 6

What is an agonist?

Answer 6

A ligand that activates a receptor.

Question 7

What is an antagonist?

Answer 7

A ligand which acts like the agonist by binding to the receptor. Antagonists do not elicit any response, however they do not ‘switch off’ a process which is usually on as well. Their sole purpose is to block the receptor from binding to an agonist.

Question 8

What are the roles of receptors?

Answer 8

Signalling by hormones, local mediators and neurotransmitters.
Cellular delivery
Control of gene expression
Cell adhesion
Modulation of the immune response
Sorting of intracellular proteins
Release of intracellular calcium stores. (Ryanoidine receptor for example.)

Question 9

How does the affinity of ligand to receptor binding differ to substrate to enzyme binding?

Answer 9

Ligand to receptor binding affinity is usually much higher.

Question 10

Give 2 examples of acetylcholine receptors.

Answer 10

Muscarinic

Nicotinic

Question 11

What is the agonist of a muscarinic ACh receptor?

Answer 11

Muscarine and also acetylcholine

Question 12

What is the agonist of a nicotinic ACh receptor?

Answer 12

Nicotine and also acetylcholine

Question 13

What are the muscarinic receptor subtypes?

Answer 13

M1
M2
M3

Question 14

What is the difference between a receptor and an acceptor?

Answer 14

Receptor:
Silent at rest
Agonist binding stimulates a biological response
Acceptor:
Operate in the absence of a ligand
Ligand binding alone produces no response

Question 15

Give examples of signal transduction. (Receptors)

Answer 15

Membrane-bound receptors with integral ion channels
Membrane-bound receptors with integral enzyme activity
Membrane-bound receptors which couple to effectors through transducing proteins
Intracellular receptors

Question 16

Outline the structure of a nicotinic acetylcholine receptor.

Answer 16

5 subunits (2 alpha, 1 beta, 1 gamma, 1 delta)
In the middle of these subunits there's a channel with a pore and a gate. In the absence of acetylcholine the gate is closed. When acetylcholine binds to the receptor it opens and allows positively charged ions to pass. Positively charged ions because the channel itself is negatively charged.

Question 17

Give examples of membrane-bound receptors with integral ion channels.

Answer 17

Nicotinic acetylcholine receptors
Gamma amino butyric acid (GABA) receptors
Glycine receptors
Glutamate receptors

Question 18

Inositol 1,4,5-triphosphate (IP3) receptors are also membrane bound receptors with integral ion channels. How do they differ from the other receptors mentioned?

Answer 18

The other receptors are on the plasma membrane of the cell. IP3 receptors are found on the endoplasmic reticulum membrane inside the cell.

Question 19

Give examples of non-classical ligand-gated ion channels.

Answer 19

ATP-sensitive K+ channels
Purinoceptors
Ryanodine receptors (activated by Ca2+)

Question 20

Give examples of membrane-bound receptors with integral enzyme activity.

Answer 20

Atrial natriuretic peptide (ANP) receptors

Growth factors receptors (insulin, epidermal growth factor, platelet-derived growth factor)

Question 21

How does signalling via tyrosine kinase-linked receptors work?

Answer 21

Tyrosine kinase phosphorylates. So as an agonist binds to the receptor site of the membrane-bound receptor with integral enzyme activity tyrosine kinase will phosphorylate the catalytic domain of the receptor that is inside the cell. An enzyme can now recognise the domain and bind to it.
It is also possible that a transducer binds to it in order for a lot of enzymes to bind to the transducer.

Question 22

What are membrane-bound receptors that signal through transfusing proteins?

Answer 22

These are seven transmembrane domain receptors which are also called GPCRs or g-protein coupled receptors.

Question 23

What is the structure of a GPCR?

Answer 23

A N-terminal on the outside.
Seven domains in total inside the membrane. Ligands can both bind to the intramembranous domain and the N-terminal.
On the inside of the cell there is a G-protein coupling domain also called a transducer.

Question 24

How does noradrenaline work in cardiac pacemaker cells? (What receptor does it bind to and what is the clinical effect?)

Answer 24

Noradrenaline binds to b1-adrenoceptors in the heart and increases the heart rate (tachycardia)

Question 25

How does acetylcholine work in the cardiac pacemaker cells? (What receptors does it bind to and what is the clinical effect?)

Answer 25

Acetylcholine binds to muscarinic receptor 2 (M2) which causes an inhibitory effect (still an agonist!) and slows down the heart rate.