Drug receptors

Question 1

Five classes of receptors

Answer 1

1. Intracellular
2. TK
3. Cytokine
4. Ion channels
5. G-protein

Question 2

Intracellular receptors must be

Answer 2

lipophilic

Question 3

Example of drugs that bind to lipophilic receptors

Answer 3

T4
Vit D
Cortisol

not easily transported in the blood -needs protein

Question 4

Intracellular receptors are inactive in

Answer 4

cytoplasm and active when ligand binds

Question 5

Drugs that bind to intracellular receptors requires time to

Answer 5

take effect

Question 6

Sequence of TK receptors

Answer 6

1. Binding of ligand to extracellular domain
2. Sub domains dimerize
3. TK self phosphorylates
4. Then TK phosphorylates down stream proteins for further signaling.

Question 7

Examples of things that bind to TK receptors

Answer 7

1. Insulin
2. EGF
3. Atrial natriuretic peptide

Question 8

Tyrosine kinase receptors and cancer

Answer 8

Overstimulation of EGF is thought to lead to cancer. These TK receptors can be blocked with monoclonal antibodies, which make the receptors dysfunctional. The antibodies bind to the extracellular domain because they would be impossible to go through the cell.

Question 9

Adding elements such as a Chloride ion or Fluoride ion can

Answer 9

increase lipophilicity of a molecule

Question 10

Cytokine receptors

Answer 10

Similar to TK receptors, but different in the fact that the intracellular domains actually recruits a TK from the cytoplasm that works as a TK through dimerization. The intracellular domain is not TK itself, but through dimerization can cause structural changes to intracellular domain that leads to the recruitment of molecules that work as TK to phosphorylate other proteins.

Question 11

Examples associated with cytokine receptors

Answer 11

1. GH
2. Interferon
3. Erythropoietin

Question 12

Ion channels

Answer 12

two main subtypes

1. Ligand gates
2. Voltage gated

Question 13

Ligand gated ion channels

Answer 13

The receptor is a pore surrounded by transmembrane proteins. For the pore to open, there must be a molecule to bind to one of the proteins for a certain ion to get into the cell.

Question 14

Example of ligand gated ion channel that allows that passage of cations

Answer 14

Nicotinic receptors

Question 15

Nicotinic receptors, what they use and how they work

Answer 15

Binds Ach and allows the influx of either sodium or calcium which leads to the depolarization of the resting potential. There are two types of nicotininc receptors, homo and heteromeric. Homo is 5 alpha whereras hetero is alpha and beta.

Question 16

In the NMJ, there will be

Answer 16

gamma subunits , whereas in the CNS, there will be alpha and beta

Question 17

Ligand gated receptor that is selective for chloride ions

Answer 17

GABA-A receptors -proteins will affect which type of drugs bind to these receptors, Same structure as nicotinic receptors

Question 18

Receptor that is composed of only two subunits

Answer 18

NMDA

Question 19

Ionotropic receptors

Answer 19

Nicotinic and GABA-A

Question 20

Cationic receptors

Answer 20

nAch receptors
Zinc activated ion channels
5-HT3 receptors

Question 21

Anionic Receptors

Answer 21

GABA-A and Glycine receptors

Question 22

Voltage gated ion channels

Answer 22

Opening follows a change in membrane potential, nothing binds to the surrounding protein. (Neural and cardiac-(Verapamil)

Question 23

Most common receptor

Answer 23

G protein

Question 24

Sequence of G protein activation

Answer 24

1. Ligand binds to extracellular domain.
2. Structural changes in the intracellular part leads to binding of GTP instead of GDP. There is normally a very high concentration of GTP compared to GDP in the cell, but when the structural change occurs after binding of the ligand, the GTP actually binds easily to the G alpha subunit replacing the GDP.
3. This GTP leads to the ceasing of the interaction between the G alpha and G beta gamma subunits (split). At this point, certain subunits of the G alpha and G beta gamma gets exposed which leads to activation certain enzymatic activities such as phosphorylation. This leads to further activation of down stream events.

Question 25

G protein has which domains

Answer 25

Extra and intracellular and transmembrane domains

Question 26

How is the G protein receptor inactivated?

Answer 26

It is not simple replacement of GTP by GDP. GTP is present at a very high concentration compared to GDP, so replacing GTP by GDP would be very unlikely. What happens is that one of the elements of G-alpha works as a GTP-ase which removes the inorganic phosphate and transforming it into GDP.

Question 27

Metabotropic receptors

Answer 27

Beta-adrenoreceptors
Muscarinic Ach receptors
GABA-B
Glucagon receptors
Certain types of serotonin and dopamine receptors

Question 28

GABA-A receptor is

Answer 28

ionotropic

Question 29

GPCR- can be regulated by ? and how?

Answer 29

Regulated by Beta arrestin binding to the intracellular domain of the receptor. This leads to endosome formation which will retrieve the receptors from the membrane.

Question 30

Gs proteins activation leads to

Answer 30

activation of Adenyl Cyclase, an enzyme that converts ATP to cAMP. cAMP works as a secondary messenger.

ATP —Adenyl Cyclase–> cAMP.

Question 31

Activation of PLC (phosphoinositide-specific phospholipase) leads to

Answer 31

leads to cleavage of phospholipids that forms Diacylglycerol (DAG) and Inositol-1,4,5-triphosphate (IP3). These are secondary messengers.

Question 32

Proteins that regulate GPCRs

Answer 32

RGS proteins

These stimulate GTPases which remove a phosphate from GTP, therefore inhibiting the RGS protein would allow for less stimulation of GTPases thus would be more more GTP to activate.

Question 33

General rule of metabolism

Answer 33

make things more polar

Question 34

Some drugs cant be used orally because of a phenomenon known as the

Answer 34

First pass effect.