block 1

Question 1

agonist

Answer 1

substance that binds to a receptor producing a response
-specifity for their receptor= lock and key

Question 2

occupancy

Answer 2

proportion of receptors occupied, varies with the agonist concentration
= number of receptors occupied/total number of receptors
-varies between 0 to 1 (full occupancy)

Question 3

how aganist levels affectv occupancy

Answer 3

-adding a low amount of agonist=low occupancy=small response
-large amounts of agonist=high
occupancy=large response
IN THEORY

Question 4

0how can occupancy be directly measured

Answer 4

via radioland binding (radiolabelled agonist)
-prepare cells by isolating them
-e.g. guinea pig ileum
- add the cells/membranes into multiple tudes or wels
-add radiolabeled agonist to the samples covering a wide range of concentrations and equilibraite (reaching equilibrium means allowing enough time for the binding reaction between the radiolabeled agonist and the receptors to reach a stable state. At this point, the rate at which the agonist binds to the receptors equals the rate at which it dissociates (unbinds), so the number of bound receptors stays constant.)
when equilibrated remove unbound drug by filtration and the bond drugs remains attached to the cells/membranes on filter
-count radioactivity of filter
-

Question 5

how can you measure non -specific binding using radioactive ligands

Answer 5

-repeat the process as normal
-but in the presences of a saturated concentration of unlabeled agonist
-that way the radioactive ligand can only bind to non-specific cites
-to obtain specific binding curve= total bound- non specific

Question 6

why do we plot radioligands on a semi-log plot?

Answer 6

Wide Range of Concentrations

Semi-log scales can display a large range of ligand concentrations compactly, making analysis easier.
S-Shaped Binding Curve (Sigmoidal)

A semi-log plot produces an S-shaped curve, which helps visualize the half-maximal binding (Kd).
Improved Resolution at Low Concentrations

Low concentrations are spread out on the log scale, enhancing visibility of initial binding events.
Linear Region for Easy Analysis

The central part of the semi-log curve is nearly linear, simplifying Kd estimation.
Enhanced Detection of Multiple Binding Sites

Helps distinguish between low- and high-affinity binding, useful for complex receptor studies.

Question 7

langmuir equation

Answer 7

-a simple equation to the binding of molecules to surface receptors

Question 8

assumption of the langmuir equation

Answer 8

-agonist to receptor interactions are at a equilibrium
-formation of agonist-receptor complex does not reduce the agonist concentration a agonist conc is in great excess

Question 9

see notes for languimer equation details

Answer 9

see notes for this whole lecture

Question 10

EC50

Answer 10

effective concentration giving 50% of maximal response
-a measure of agonist potency

Question 11

receptor reserve

Answer 11

not all receptors occupied to give maximal response-amplification of siginals

Question 12

potency

Answer 12

a measure of how much of a drug or substance is needed to produce a certain effect.
-A high-potency drug needs only a small amount to have an effect, while a low-potency drug requires a larger amount to achieve the same effect.

Question 13

advantages of signaling amplification and reserve receptor

Answer 13

-physiological efficient as a small amount of agonist concentration can cause maximum response
-loss of receptors with age or disease conditions does not readily lead to loss of cell or organ performance

Question 14

fitting curve respose

Answer 14

-see variation of Langmuir equation i notes

Question 15

kd value

Answer 15

concentration when half the receptors are occupied

Question 16

Emax

Answer 16

-measures efficancy
- the greatest possible effect a drug or substance can produce, no matter how much more of it you add.

Question 17

partial agonist

Answer 17

ave less intrinsic efficacy than full agonists; may stimulate a
partial or full maximal response (Emax) depending upon number of receptors in
that cell type

Question 18

antagonist

Answer 18

drug that prevents a biological response

Question 19

chemical antagonism

Answer 19

-antagonist combines with or chemically modifies an active drug so that the effects of the active drug are lost.

Question 20

pharmacokinetic antagonism

Answer 20

• reduces the amount of drug absorbed, e.g. decreased absorption from the GI tract, such as by altering gut motility
  -change in the rate of renal excretion of a drug
  -change in drug metabolism

Question 21

physiological antagonism

Answer 21

The interaction of two drugs with opposing cellular or organ
responses in the body
e.g. - histamine causes contraction of smooth muscle in
airways smooth muscle (H1 receptors) and thus
bronchoconstriction; adrenaline causes the opposite effect
(via β2 receptors): relaxation of the smooth muscles and
bronchodilation
Used to describe opposing actions of 2 drugs through
different transduction/receptor systems in the same cell or
different cell types in one organ

Question 22

antagonism of signalling events

Answer 22

blocks some stepp in the process between receptor activation and response. it does not compete with the agonist for the receptor site

Question 23

competitive antagonist

Answer 23

binds to the receptor;but has no response

Question 24

reversible competitive antagonist

Answer 24

• the effects of the antagonist can be reversed or washed off

Question 25

irreversible competitive antagonist

Answer 25

when the antagonist dissociates from the receptor slowly or not al all, in some cases the antagonist may chemically bind to the receptor

Question 26

concentration-response curve for a competitive antagonist

Answer 26

-parallel rightward shift but no change in the max

Question 27

concentration response graph for an irreversible antagonist

Answer 27

Irreversible Competitive Antagonist:

This type of antagonist binds permanently (or very tightly) to the receptors, blocking them from being activated by the agonist.
Since this binding is irreversible, once the antagonist is bound, that receptor is “out of commission” for good.
Time-Dependent Effect:

When you first add an irreversible antagonist, some receptors get blocked, but there are still many unblocked receptors available.
Initially, if you add more agonist, it can activate the remaining receptors, allowing you to reach the full response, Emax.
This is why you see a parallel rightward shift on the graph (you need more agonist to achieve the same response, but you can still reach Emax at the start).
As Time Passes – Gradual Decrease in Available Receptors:

Over time, more and more receptors are blocked by the irreversible antagonist.
Eventually, there aren’t enough unblocked receptors left for the agonist to produce the full response, so Emax begins to decrease.
This is seen as a downward shift in the maximum response on the graph.
Final Stage – No Response:

If enough receptors are blocked by the antagonist over time, the agonist may no longer be able to produce any response, no matter the concentration.
On the graph, this would look like a continuing drop in Emax until it reaches zero, meaning no response can be evoked.

Question 28

dose ratio

Answer 28

how many fold greater agonist concentration is needed in the presence of an antagonist to stimulate the same response

Question 29

dose ratio equation

Answer 29

agonist EC50 in presence of antagonist/agonist EC50 in absence of antagonist

Question 30

pA2 values for antagonists (a measure of antagonist potency)

Answer 30

= -log10(A2)
a2 value= molar concentration of antagonist that gives a dose ratio of 2
-high Pa2 value mans the antagonist are more potent than antagonist with low pA2 values

Question 31

log of the schild equation

Answer 31

log10(DR-1)=log10(XB)-logKb
-pA2 is minus the y intercept
e.g y intercept=8.5 pa2 value=-8.5