Biological Signalling And Receptors - Drug Targets

Question 1

Define a receptor

Answer 1

A molecule thatrecognises a second molecule being a ligand or family of molecules - results in a regulation of cellular processes.

Question 2

What is a ligand

Answer 2

Any molecule that binds specifically to a receptor site

Question 3

When is a ligand termed a an agonist

Answer 3

When it binds to a receptor , activating it

Question 4

When is a ligand termed an antagonist

Answer 4

• when it binds to a receptor without causing activation.

Question 5

What is paracrine signalling ?

Answer 5

The signalling molecules released by a cell affect target cells in close proximity to it.An example would be synaptic or neuromuscular junctions

Question 6

What class of molecules would bind to cell surface receptors ?

Answer 6

Hydrophilic

Question 7

What class of molecules would bind to intracellular receptors ?

Answer 7

• hydrophobic molecules for example steroid hormones such as oestrogen.

Question 8

Is ligand binding affinity of ligand binding at receptor sites or binding of substrates have a higher affinity

Answer 8

• Ligand binding at receptor sites has a greater affinity than enzyme - substrate binding because it has a lower ‘ Kd’

Question 9

What are the two types of ACH receptors ?

Answer 9

1) nicotinic ACH receptors

2) Muscarinic ACH receptors

Question 10

What is an example of membrane bound receptors with integral ion channels?

Answer 10

• nicotinic ACH receptors that have a gated sodium , potassium and calcium channels.
• Glycine receptor which has a gated chloride channel.

Question 11

What is an example of membrane bound receptors with integral enzyme activity ?

Answer 11

Insulin receptors which is directly linked to the enzyme : tyrosine kinase.

Question 12

How does the insulin receptor work ? ( membrane bound receptors with integral enzyme activity )

Answer 12

1) insulin binds to receptor tyrosine kinase
2) the receptors then dimerise ( pair up)
3) the paired receptors phosphorylate eachother on tyrosines in the intracellular domain.
4) this then results in a cellular response.
4) this then goes on to activate more enzymes and DNA transcription factors are made which are used to make GLUT2 channels which help with the transport of glucose.

Question 13

What is an example of membrane bound receptors which couple to effectors through transducing proteins ?

Answer 13

• Muscarinic ACH receptors

Question 14

What are intracellular receptors

Answer 14

• receptor proteins found on the inside of a cell , typically in the cytoplasm or nucleus.
• in most cases , the molecules are hydrophobic as they must be able to pass the bilayer of the membrane.
• examples are steroid hormones such as oestrogen , progesterone , cortisol
  1) when a hormone enters a cell and binds to the receptor , it causes the receptor to change shape - allowing the receptor-hormone complex to enter the nucleus.
  2) the receptor-hormone complex then can regulate gene activity by binding to specific sequences in the DNA as hormone binding exposed regions of the receptor that have DNA binding activity.

Question 15

What are the 4 major classes of membrane bound receptors ?

Answer 15

1) intracellular receptors
2) membrane bound receptors with an ion channel
3) membrane bound receptors with integral enzyme.
4) membrane bound receptors via G-coupled protein receptors

Question 16

Name a therapeutic drug that acts on the nicotinic ACH receptors ?

Answer 16

• succinylcholine
• this acts by binding to the ACH receptors , causing a conformational change in the Na+ channel.
• depolarisation occurs.
• ACH esterase cannot break down sunccinylcholine.
• remains in the fixed depolarised state , Na+ channels become inactivated.
• so a wave of depolarisation cannot occur.

Question 17

Where is the Muscarinic ACH receptor found ?

Answer 17

• between the post ganglionic neurone and effector tissue ( eg smooth muscle , gut , heart)
• mainly in the parasympathetic nervous system , with the only exemption being sweat glands in the sympathetic nervous system.

Question 18

Name a therapeutic drug that acts on Muscarinic ACH receptors?

Answer 18

• Atropine ( antagonist)
• binds to M2 receptors in the heart - prevents ACH from binding.
• this causes the heart rate to increase causing tachycardia .

Question 19

What is the main difference between ACH receptors and insulin receptors to receptors for oestrogen ?

Answer 19

Insulin & Ach receptors have an extracellular receptor binding site, whereas oestrogen receptors are intracellular.

Question 20

are all receptors specific ?

Answer 20

No , for example Nicotinic ACH receptors have gated Na+, k+ and Ca2+ channel s.