Drug targets

Question 1

Name 6 ligand gated ion channels

Answer 1

• GABA A
• neuronal nACHR
• muscarinic nACHR
• Serotonin type 3 receptor
• glycine receptor

-ionotrophic glutamate receptor

Question 2

Describe the structure of a muscle nicotinic acetylcholine receptor

Answer 2

• pentanoic with 5 sub units
• adult muscle has 2 alpha, 1 beta, 1 delta and 1 epsilon
• fetal muscle differs in that the 1 epsilon subunit is replaced with a gamma subunit
• each subunit has 4 transmembrane domains
• second tm domain is the lining of the ion channel
• the agonist binding site is within the large extracellar N terminus
• the large loop between tmd 3 and 4 interacts with cytoskeleton and is the target for regulatory proteins

Question 3

Decribe the differences in structure of nicotonic actelycholine recpetors in mucle, brain, GI and heart

Answer 3

muscle: 2 alpha, 1 beta, 1 delta, 1 epsilon
brain: 3 beta 2 subunits, 2 alpha 4 subunits
GI and Heart: 3 beta 4 subunits, 2 alpha 3 units

Question 4

How does nicotine affect the body and could it help any disease in any way?

Answer 4

-affects brain, heart, GI tract but not muscle
if could select for brain rather than cardiovascular, could be beneficial for treatment of some diseases such as Parkinsons

Question 5

Name the 3 types of voltage gated receptors

Answer 5

• sodium
  -calcium
  -potassium
  all tetrameric
  although na and ca are in one long protein

Question 6

Describe the structure of the sodium/ calcium receptors

Answer 6

small beta subunit
alpha subunit split into 4 pseudosubunits
each pseudosubunit has 6 transmembrane domains
24 in total
each have a dipping between 5th and 6th transmembrane domains which come together to form lining of channel
when membrane potential changes, 4th tmd moves in reaction- opening or closing the channel

Question 7

State the different types of calcium channels

Answer 7

-L type, N,P,Q,R,T
L antagonists are useful cardiovascular drugs
N and P antagonists are neurotoxins

Question 8

Bensodiazeprine agonists

Answer 8

GABA recptors
alpha selective: hypnotics
alpha 2,3 nd 5 selectives: anxiolytics

Question 9

Where are nuclear hormone receptors usually found?

Answer 9

the cytoplasm

Question 10

What is an orphan receptor

Answer 10

a receptor for which the endogenous ligand is not known

Question 11

Phospholipase is linked too…

Answer 11

Gq

Question 12

Which receptor class is most frequently targeted by drugs?

Answer 12

G Protein-coupled receptors

Question 13

The G protein Gq is coupled to…

Answer 13

phospholipase C

Question 14

what is transactivation

Answer 14

the process by which nuclear hormone receptors increase expression of a protein
-nuclear hormobe receptors bind to ligand, dissociate from heat shock proteins and dimerize before entering nucleaus.

Question 15

G protein Gi is coupled to..

Answer 15

adenylate cyclase (negatively)

Question 16

G protein Gs is coupled to…

Answer 16

adenylate cyclase (positively)

Question 17

What is a G protein

Answer 17

a protein that links receptors to intracellular signalling pathways
g proteins are trimeric- they have an alpha beta and gamma subunit.
They have buily in GTPase enzyme activity

Question 18

what is transrepression

Answer 18

the process by which nuclear hormone receptors decrease expression of a protein

Question 19

What is IP3

Answer 19

inositol trisphosphate is a secind messenger produced in the phospholipase c pathway
It is coupled to Gq

Question 20

Give an example of 3 cell surface receptor proteins

Answer 20

GABA
mucarinic actylcholine receptor
nicotinic acetylcholine receptor

Question 21

Give some examples of nuclear hormone receptors

Answer 21

Sex hormone receptors
Thyroid hormone receptor
Corticosteroid receptors
Vitamin D receptor
Retinoic acid receptors

Question 22

Give some common examples of drugs acting via GPCRs

Answer 22

-antidepressants
-antipsychotics
-anti-asthma e.g. salbutamol
-glaucoma- pilocarpine
bp- losartan, atenolol

Question 23

Describe the diversity of G Protein coupled receptor subunits

Answer 23

Muscarinic- m1-m5

adrenergic receptors- alpha 1, alpha 2, beta 1 beta 2

Question 24

Signals coupled to cAMP

Answer 24

Adrenaline/Noradrenaline
Glucagon
Dopamine
Somatostatin
Parathyroid hormone
(+ many others)

Question 25

How is cAMP produced?

Answer 25

Cyclic AMP is produced from ATP by the enzyme adenylate cyclase (aka adenylyl cyclase).

Question 26

What is the main effect of cAMP?

Answer 26

cAMP’s main effect is to switch protein kinases from an inactive to an active conformation

Question 27

What are the functions of kinases and phosphotases?

Answer 27

Protein kinases phosphorylate proteins at specific sites to regulate their activity. A corresponding set of enzymes, phosphotases, remove phosphate groups from proteins.

Question 28

How is the production of cAMP regulated?

Answer 28

Often, the production of cAMP is regulated by GPCRs. A particular type of G-protein known as Gs (stimulatory) enhances the activity of adenylate cyclase. Gs differs from other G-proteins because it contains the alpha s subunit.

Question 29

Name a few cAMP regulated enzymes

Answer 29

Protein kinase A
glycogen synthase
pyruvate kinase
histones (DNA

Question 30

Signals coupled to IP3/phospholipase C

Answer 30

Acetylcholine (muscarinic receptor)
Adrenaline/Noradrenaline
Vasopressin
Serotonin

Question 31

Various types of antagonism

Answer 31

Orthosteric (competitive)
Allosteric (non-competitive)
Functional
Indirect