Drug targets Flashcards
(31 cards)
Name 6 ligand gated ion channels
- GABA A
- neuronal nACHR
- muscarinic nACHR
- Serotonin type 3 receptor
- glycine receptor
-ionotrophic glutamate receptor
Describe the structure of a muscle nicotinic acetylcholine receptor
- 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
Decribe the differences in structure of nicotonic actelycholine recpetors in mucle, brain, GI and heart
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
How does nicotine affect the body and could it help any disease in any way?
-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
Name the 3 types of voltage gated receptors
- sodium
-calcium
-potassium
all tetrameric
although na and ca are in one long protein
Describe the structure of the sodium/ calcium receptors
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
State the different types of calcium channels
-L type, N,P,Q,R,T
L antagonists are useful cardiovascular drugs
N and P antagonists are neurotoxins
Bensodiazeprine agonists
GABA recptors
alpha selective: hypnotics
alpha 2,3 nd 5 selectives: anxiolytics
Where are nuclear hormone receptors usually found?
the cytoplasm
What is an orphan receptor
a receptor for which the endogenous ligand is not known
Phospholipase is linked too…
Gq
Which receptor class is most frequently targeted by drugs?
G Protein-coupled receptors
The G protein Gq is coupled to…
phospholipase C
what is transactivation
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.
G protein Gi is coupled to..
adenylate cyclase (negatively)
G protein Gs is coupled to…
adenylate cyclase (positively)
What is a G protein
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
what is transrepression
the process by which nuclear hormone receptors decrease expression of a protein
What is IP3
inositol trisphosphate is a secind messenger produced in the phospholipase c pathway
It is coupled to Gq
Give an example of 3 cell surface receptor proteins
GABA
mucarinic actylcholine receptor
nicotinic acetylcholine receptor
Give some examples of nuclear hormone receptors
Sex hormone receptors Thyroid hormone receptor Corticosteroid receptors Vitamin D receptor Retinoic acid receptors
Give some common examples of drugs acting via GPCRs
-antidepressants
-antipsychotics
-anti-asthma e.g. salbutamol
-glaucoma- pilocarpine
bp- losartan, atenolol
Describe the diversity of G Protein coupled receptor subunits
Muscarinic- m1-m5
adrenergic receptors- alpha 1, alpha 2, beta 1 beta 2
Signals coupled to cAMP
Adrenaline/Noradrenaline Glucagon Dopamine Somatostatin Parathyroid hormone (+ many others)
