Receptors Flashcards
Partial agonist?
Binds and activates receptor. Partial efficacy compared to a full agonist even at maximal receptor occupancy
Inverse agonist?
Bonds to same receptor site as agonist.
Inhibits constitutive activity of receptor.
Exerts opposite response to agonist.
Prerequisite for inverse agonist?
The receptor must have a constitutive activity in the absence of an agonist
Potency of agonist?
Half the maximal effective concentration of agonist- EC(50)
Relationship of EC(50) and potency?
The smaller the EC(50) the more potent the agonist
List the 4 receptor types
LGIC
GPCR
single transmembrane receptor
Intercellular receptor
How is the margin of safety of a drug evaluated?
By the therapeutic index.
TC(50)/EC(50
The bigger the better
Difference between drug specificity and selectivity?
Drug selectivity:
Drug has greater affinity for one receptor over another.
Other receptor still has some binding and activity.
Drug specificity:
No increase in drug can activate the other receptor
What types of LGICs are there?
Pentameric
Tetrameric
Trimeric
Give examples of pentameric LGICs.
Nicotinic ACh
GABA (A)
Glycine
Serotonin (3)
Give an example of a tetrameric LGIC
Glutamate
Give an example of a Trimeric LGIC
ATP
How many transmembrane helices are in a GPCR?
7
Where is the N terminus and C terminus positioned on a GPCR?
N terminus is extracellular
C terminus is intercellular
How much time does it take to activate a LGIC
Less than one millisecond
How much time does it take to activate a GPCR?
Seconds to minutes
4 types of G proteins
S
I
O
Q
What does Gs do?
Stimulates AC
What does Gi do?
Inhibits AC
What does Go do?
Stimulate PLC-beta
What does Gq do?
Stimulate PLC-beta
What’s a full agonist?
A ligand which binds and activates a receptor, producing maximal efficacy at that receptor
What are the key events in tyrosine kinase activation?
Ligand binds to extracellular receptor domain
2 receptors dimerise
A conformational change of the intracellular kinase domains renders the active sites available for autophosphorylation by ATP
Where in the cell are steroid receptors found?
In the cytosol
What macromolecule do steroids activate?
DNA
Where is the dose response curve of a ligand more potent than another?
Closer to zero on the x axis
What’s different about the dose response curve of a ligand with a greater efficacy than another?
It is longer on the y axis
How does the Castillo & Katz mechanism explain how a partial agonist operates?
It shows that a ligand can be bound to a receptor without it activating it.
If the efficacy at a receptor is 1, what is the efficacy of an antagonist at that receptor?
The efficacy of an antagonist is always 0.
What is the pA(2) of an antagonist?
It’s the antagonist potency
=-logK(b) for a competitive antagonist
How is the pA(2) evaluated?
Does not depend on K(A)
Increases linearly with x(B)
Slope of plot of (r(A)-1) against x(B) is 1/K(B)
Relationships independent of agonist characteristics
Should be the same for all agonists on the same population of receptors
