Flip the classroom sessions
PD
1. At a concentration of 10-9 M, a full agonist A produces 50% of its maximum effect on
smooth muscle. Another agonist B with an intrinsic activity of 0.6 produces (at 10 -8 M),
only 30% of the maximally possible effect of activation of this receptor.
a. What are the pD2 values of the agonists?
(a) pD2 = -log [10-9] = 9.
(b) pD2 = -log [10-8] = 8.
b. What pA2 value does antagonist C have who (at a concentration of 10 -6 M) causes a
shift of the dose-response curve of A by a factor of 30?
pA2 = log ((X2/X1) -1) – log Y.
log 30 + 6 = 7.5.
c. On graph paper, sketch as accurately as possible the dose-response curves for agonist
A, in the absence and presence of 10-6 M of antagonist C, respectively.
For the effect of agonist X, whether or not in the presence of a full antagonist Y, the
following applies:
E x,y αx
--------- = ------------------------------------------------------
E max 1 + (1+ [Y]/Kd y) . Kdx2/[X]
2. In experiments investigating the pharmacological properties and function of
adrenoreceptors, an intravenous infusion of isoprenaline in a rat produces a dose-
dependent increase in heart rate and blood pressure.
Isoprenaline is a non-selective adrenoreceptor (B1 and B2) agonist that leads to an
increase in heart rate and blood pressure.
a. What mechanisms (receptors, organs) explain these observations?
Beta 1 receptor is primarily expressed in the heart and increases contraction force.
Beta 2 is expressed in smaller arteries/ arterioles, activation leads to dilation of
peripheral blood vessels (but beta 1 compensates for this!). So, beta 1 causes the
overall effect.
b. What would you expect to happen in the cardiovascular system, if instead of
isoprenaline an infusion of noradrenaline was to be administered?
Noradrenaline also actives adrenoreceptors, noradrenaline will activate certain
subtypes of adrenoreceptors at a lower concentration because it has the highest
affinity for alpha 1 adrenoreceptor (not expressed in the heart).
> increased heart pressure, but the system will react by lowering the contraction rate/
force > thereby compensating and lowering the blood pressure back to normal levels
> NO overall effect on blood pressure.
c. What effects would you expect on the iris of the eye and on the bronchial muscles in
the lungs during these experiments?
Affinity isoprenaline too low to have an effect on the iris.
Activation of beta 2 receptors > will lead to relaxation of bronchial muscle cells >
widening of the bronchi.
For NA: NA high affinity for alpha 1 so > pupils will widen.
At higher concentration NA can also activate beta 2 receptors > dilation of bronchial
muscles and muscle widening of the bronchi.
3. Reserpine is a drug that was used to treat high blood pressure. One of the effects of
reserpine administration is a significant reduction in the amount of monoaminergic
neurotransmitters (especially dopamine, noradrenaline and serotonin) in the central and
PD
1. At a concentration of 10-9 M, a full agonist A produces 50% of its maximum effect on
smooth muscle. Another agonist B with an intrinsic activity of 0.6 produces (at 10 -8 M),
only 30% of the maximally possible effect of activation of this receptor.
a. What are the pD2 values of the agonists?
(a) pD2 = -log [10-9] = 9.
(b) pD2 = -log [10-8] = 8.
b. What pA2 value does antagonist C have who (at a concentration of 10 -6 M) causes a
shift of the dose-response curve of A by a factor of 30?
pA2 = log ((X2/X1) -1) – log Y.
log 30 + 6 = 7.5.
c. On graph paper, sketch as accurately as possible the dose-response curves for agonist
A, in the absence and presence of 10-6 M of antagonist C, respectively.
For the effect of agonist X, whether or not in the presence of a full antagonist Y, the
following applies:
E x,y αx
--------- = ------------------------------------------------------
E max 1 + (1+ [Y]/Kd y) . Kdx2/[X]
2. In experiments investigating the pharmacological properties and function of
adrenoreceptors, an intravenous infusion of isoprenaline in a rat produces a dose-
dependent increase in heart rate and blood pressure.
Isoprenaline is a non-selective adrenoreceptor (B1 and B2) agonist that leads to an
increase in heart rate and blood pressure.
a. What mechanisms (receptors, organs) explain these observations?
Beta 1 receptor is primarily expressed in the heart and increases contraction force.
Beta 2 is expressed in smaller arteries/ arterioles, activation leads to dilation of
peripheral blood vessels (but beta 1 compensates for this!). So, beta 1 causes the
overall effect.
b. What would you expect to happen in the cardiovascular system, if instead of
isoprenaline an infusion of noradrenaline was to be administered?
Noradrenaline also actives adrenoreceptors, noradrenaline will activate certain
subtypes of adrenoreceptors at a lower concentration because it has the highest
affinity for alpha 1 adrenoreceptor (not expressed in the heart).
> increased heart pressure, but the system will react by lowering the contraction rate/
force > thereby compensating and lowering the blood pressure back to normal levels
> NO overall effect on blood pressure.
c. What effects would you expect on the iris of the eye and on the bronchial muscles in
the lungs during these experiments?
Affinity isoprenaline too low to have an effect on the iris.
Activation of beta 2 receptors > will lead to relaxation of bronchial muscle cells >
widening of the bronchi.
For NA: NA high affinity for alpha 1 so > pupils will widen.
At higher concentration NA can also activate beta 2 receptors > dilation of bronchial
muscles and muscle widening of the bronchi.
3. Reserpine is a drug that was used to treat high blood pressure. One of the effects of
reserpine administration is a significant reduction in the amount of monoaminergic
neurotransmitters (especially dopamine, noradrenaline and serotonin) in the central and
