L5- Drug-Receptor Interactions 2

Question 1

what does the graph look like for the number of ligands/m^2 against the number of receptor sites filled?

Answer 1

A rectangular hyperbola.

(like conc against effect i think)

Question 2

What is a better way to plot how conc of ligand affcts result?

Answer 2

Log scale on the x axis. This spreads out the scale and gives sigmoidal curve.

Question 3

What is Kd?

Answer 3

A dissociation constant. The concentration that gives 50% of maximal occupancy. The higher the Kd, the lower the affinity.

Question 4

What can both the equations for the binding of oxygen to haemoglobin and absorption of gases onto metalic catalysts be derived from?

Answer 4

The Law of Mass Action

Question 5

What did Clark show to prove his theory of receptors that drugs bind to?

Answer 5

1. No relationship between the amount of drug in the cell and the response
2. Drug doesn’t cover cell surface
3. Receptor concept fitted in with the emerging picture of cells

Question 6

What is the equation that describes drug biinding to a saturable site?

Answer 6

B= ( Bm x [D] ) / Kd + [D].

Bm= max binding

Kd= conc giving 50% max binding

B= drug bound

VERY IMPORTANT TO LEARN.

Question 7

On a graph of log(Drug) against drug bounds, how would you find Kd?

Answer 7

Read across from where 1/2 max binding. Then read down gives you log(Kd). Then you do 10^x of your log Kd to give you Kd.

So if logx=5. then 10^5=x

Question 8

If logKd=1, what is Kd?

Answer 8

10.

10^1=10

Question 9

How do you measure drug binding by a radioligand binding assay?

Answer 9

1. You take a cell preparation and radiolabelled version of the drug and incubate them together
2. Then have to separate the bound drug (bound to receptors on cell) from the free drug still in solution.
3. Either by filtration through glass fibre as the cells are larger. Or by centrifugation, cells will end up as pellet.

Question 10

What does Kd tell us about affinity?

Answer 10

The smaller the Kd, the higher the affinity

Question 11

What is pKd?

Answer 11

pKd= -log Kd

Question 12

What’s the advantage of using pKd?

Answer 12

avoids using very small numbers

as pKd increases, affinity increases

p=proportional

Question 13

What does the pKd tell us about affinity?

Answer 13

The bigger the pKd, the bigger the affinity

Question 14

What does [RD]/[Rt] equal?

Answer 14

not sure how… but it gets to

B=Bm.[D] / Kd+ [D]

Question 15

At Kd what is [RD]/Rt?

Answer 15

Kd/ (kd+kd) = 0.5

As Rd=0.5 x Rt

Rt=Bmax

RD= drug bound