Receptors and signalling molecules as drug targets

Question 1

What are the 4 super-families of receptors?

Answer 1

Ligand-gated ion channels
G protein-coupled receptors
Kinase-linked receptors
Nuclear receptors

Question 2

How fast does a response occur in a ligand-gated ion channel?

Answer 2

Within milliseconds

Question 3

Which ions are nicotinic acetylcholine receptors permeable to?

Answer 3

Na+, K+ and Ca2+

Question 4

What 2 full agonists act on nicotinic acetylcholine receptors?

Answer 4

Acetylcholine
Nicotine

Question 5

What is the use of varenicline?

Answer 5

It blocks nicotine binding to the α4ß2 nACh receptor and exerts partial agonist activity at the receptor. This makes it a useful drug to reduce nicotine cravings

Question 6

How fast does a response occur in a G protein-coupled receptor?

Answer 6

Within seconds

Question 7

What category of receptors are an example of G protein-coupled receptors?

Answer 7

Adrenoceptors

Question 8

What are the different types of adrenoceptor?

Answer 8

α1- adrenoceptors
α2 - adrenoceptors
ß1 - adrenoceptors
ß2 - adrenoceptors
ß3 - adrenoceptors

Question 9

What physiological effects are caused by activation of α1 adrenoceptors?

Answer 9

Vasoconstriction of blood vessels

Question 10

What physiological effects are caused by activation of α2 adrenoceptors?

Answer 10

Presynaptic inhibition of noradrenaline in the CNS and relaxation of the GI tract

Question 11

What physiological effects are caused by activation of ß1 adrenoceptors?

Answer 11

Increased heart rate and cardiac muscle contraction

Question 12

What physiological effects are caused by activation of ß2 adrenoceptors?

Answer 12

Dilation of the bronchi
increased heart rate and cardiac muscle contraction

Question 13

What physiological effects are caused by activation of ß3 adrenoceptors?

Answer 13

Thermogenesis in skeletal muscle and lipolysis

Question 14

What occurs when adrenaline binds to the ß2 adrenoceptor?

Answer 14

The receptor causes the replacement of GDP with GTP, which is connected to Gαs and Gßγ
The Gαs and GTP then activates adenylyl cyclase
This converts AMP into cAMP (cyclic)
This activates Protein Kinase A
This causes inhibition of MLCK activity which in turn causes bronchodilation

Question 15

What occurs when adrenaline binds to α2 adrenoceptors?

Answer 15

The receptor causes the replacement of GDP with GTP, which is connected to Gαi and Gßγ
The Gαi and GTP inhibit the action of adenylyl cyclase
This prevents formation of cAMP
The Gßγ stimulated the opening of K+ ion channels
These both cause relaxation of the GI tract

Question 16

What occurs when adrenaline binds to α1-adrenoceptors?

Answer 16

The receptor causes the replacement of GDP with GTP, which is connected to Gαq and Gßγ
The Gαq and GTP activate the enzyme Phospholipase C
This allows for the conversion of PIP2 to DAG and IP3
This increases levels of Ca2+
This causes vasoconstriction

Question 17

How is salbutamol used in the treatment of acute symptoms of asthma?

Answer 17

It binds to and activates ß2-adrenoceptors, leading to bronchodilation

Question 18

What occurs due to overexposure to salbutamol?

Answer 18

Receptors are down-regulated and are internalised to decrease activation of receptors
Phosphodiesterases also terminate the action of cAMP

Question 19

How is theophylline used in the treatment of COPD?

Answer 19

It is a phosphodiesterase inhibitor, so allows for continued cAMP action, meaning long lasting bronchodilation

Question 20

How long after activation, does a response occur in a kinase-linked receptor?

Answer 20

In hours

Question 21

What occurs in response to activation of an insulin kinase-linked receptor?

Answer 21

Insulin binds to the receptor and causes a conformational change
This allows binding of relay proteins to the protein kinases
This allows many different cellular responses

Question 22

What is an example of a nuclear receptor?

Answer 22

Steroid receptors

Question 23

How do steroid receptors work?

Answer 23

Steroid hormones can pass through the cell membrane
Here, they bind to the steroid receptors
This complex then moves through the nuclear pores and into the nucleus
Here, it binds to a ligand-binding domain sites on chromatin, activating transcription

Question 24

What is the use of Sodium valproate?

Answer 24

It is a broad spectrum anti-epileptic drug

Question 25

How does sodium valproate work?

Answer 25

It is a weak inhibitor of GABA transaminase, increasing GABA levels.
GABA is a inhibitory neurotransmitter
It is also an inhibitor of succinic semialdehyde dehydrogenase, which indirectly increases GABA levels
It also has other means of increasing GABA levels and decreasing nerve stimulation that causes seizures

Question 26

What are the uses of Ethosuximide?

Answer 26

They are used to treat one absence seizures

Question 27

What is the method of action of ethosuxamide?

Answer 27

It blocks off T-type voltage gated Ca2+ channels in the synaptic knob

Question 28

What is serotonin also known as?

Answer 28

5-HT

Question 29

What is an SERT?

Answer 29

A seretonin transporter

Question 30

What is an SSRI?

Answer 30

A selective seretonin reuptake inhibitor

Question 31

What are some examples of SSRIs?

Answer 31

Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline

Question 32

How many proteins form the Nicotinic Acetylcholine receptors?

Answer 32

5