DR _ __

D + R DR(activated)--.-. measured response

affinity
efficacy

The measured responses to varying drug concentrations can be plotted against

concentration on either a linear or logarithmic scale 1• The data is identical in both cases -
it is just the representation that is different. On a linear scale the lower concentrations
appear squashed close to the y-axis whereas on the logarithmic scale the data points are
more spread out. The logarithmic representation is the one that is most commonly used.

Linear scale Logarithmic scale

120
120
100
100
response
80 respons
730

60 j
60
I
•o ' 40

20 j 20

0 0
0 1x10·6 2x!O·• 3x10_. 4x10·6 Sx10·6 lx10·8 lx!0·7 lxJ0-6 lx!0·5
[Agonist drug] (M) [Agonist drug] (M)

1
A note about log scales and using log graph paper is in Appendix I.
 A. 0 oresponse
Sketch responses for the following 100
on the graph opposite.
00

A full agonist on its own. 0J

A partial agonist on its own. 40 - ---

20
An antagonist on its own.
0 .1.......-----~- - - - - -
1 10 100 1000
(Assume that they all have similar 0
affinities for the receptor) chJy conca ltlatkln (µM)

B. Same concentration of full agonist present

Sketch the response for throughout
a fixed concentration of a o oresponse
100 - - - - - - - -
full agonist in the
presence of increasing
concentrations of a
00 _;_I-----
competitive antagonist. 1

40 0---

a> j-
I

0 10 100 1000
antaga ist CXJi ,ce, lb am.,;,

o response
c. 100 , - - - - -
Sketch the responses for
increasing concentrations of agonist 00
(1) alone and 0J -- ------
(2) in the presence of a fixed
concentration of a competitive 40 - l - - - -
antagonist. 2() + - - - -

O+---~-----~---
0 10 100 1000
agonist CXJi ,ce, t, atkJn
D.
0~
Sketch the responses for increasing 100 T
concentrations of full agonist
(1) alone
(2) in the presence of a fixed
concentration of a partial
agonist

0 10 100 1000

E. Sketch the responses for (<',response

100 ~
increasing concentrations of partial
agonist in the presence of a fixed 00
concentration of a full agonist
00

40

20

0 10 100 1000
agorisl co, IC& lbatlon

Hint: Sometimes it helps to think abo11t the extreme ends of the graph. Egfor (BJ, think abo11t what
the response wo11ld be when the antagonist concentration is zero and the f11II agonist concentration is a
certain val11e. Then what wo11ltl happen when the f11I/ agonist concentration was the same certain va/11e
b11t the antagonist concentration is very m11ch higher.

Answers to the activities are in Appendix 2.

What is the relationship between the ECso and the Kd?

The EC 50 is the concentration required for half the maximum response whilst the Kd is
the concentration required for half maximum receptor occupancy. Consider a situation
where only 20% of receptors need to be occupied in order to maximally stimulate the
response. This might occur because of signal amplification. Say one receptor can activate
many G proteins which can each activate many adenylate cyclase enzymes then it is
possible that activation of only a few receptors may cause maximum conversion of ATP
to cyclic AMP (the reaction catalysed by adenylate cyclase).

This scenario is illustrated in the figure.

The top graph illustrates 1.0

how the receptor

,
occupancy increases with 0.8 I ?'
increasing drug Proportion I /
concentration. of receptors 0.6
occupied I
/I_
with drug o. 4
In this example a /'
cqncentration of 0.2 /
5 nM is required to occupy / I

50% of receptors hence 0.0

..- 'f
~ =~ nM. 0.1 1 1000

Approximateh· 1.2 nl\f is

[drugJ (nM)
l K.i = nM
I
required to occupy 20% of
receptors.
100
I
......-- - -
([DR]/[RT] = 0.2) 80 .J.-----.,.
I /

The response is displa\·ed 60 ,---./

%of I
in the bottom graph. maximum I
40 r, I
response
In this particular example
there is significant signal 20 'L
amplification and this same 0 I 'I'
concentration o f 1.2 nM 100 1000
1~ 10
gives almost 90% of the v1 drug] (nM)
maximum respo nse.
When [D) = 12 nM,
occupancy is ~20% and
response is ~ 90%
The EC50 for the response
is~· nM.

The EC 50 is very much less than the ~-

This phenomenon is known amongst pharmacologists as "Receptor Reserve" or

sometimes (1n older textbooks) "Spare Receptors".

Biochemists are more likely to call it "signal amplification".