L6 SCHILD Flashcards
For lab 3 (23 cards)
What do competition binding studies identify?
Receptors but do not show cellular function of receptor subtype.
What is measured to assess receptors that mediate a function?
Cellular responses downstream of receptor activation.
What does Schild analysis recognize?
Receptors involved in agonist induced responses through receptor selective competitive antagonist.
What is an orthosteric antagonist?
A receptor selective competitive antagonist.
What happens when an agonist and antagonist compete for a receptor?
The chemical forces in drug binding are weak and reversible.
What is the typical binding behavior of receptors like β1?
Bind one drug at a time, demonstrating competition.
What occurs to the fraction of receptors occupied by the agonist as antagonist concentration increases?
It decreases.
What does a high affinity antagonist indicate?
A low K(b) value.
What is the effect of an antagonist on dose-effect curves?
Shifts the curves rightward.
What does the dose ratio (DR) represent?
The ratio of concentrations that produce the same effect in presence and absence of a competitive antagonist.
What is the Schild equation?
Log[Kb]=Log[B]−Log(DR−1)
What does Kb represent in the Schild equation?
Affinity of antagonist.
What is the significance of the pA2 value?
Negative log of antagonist concentration causing a 2-fold shift in agonist dose-effect curve.
How is the pA2 value calculated from a Schild plot?
It is where the Schild plot intersects the x-axis.
What should the plot of log[B] vs log(DR−1) look like if it is linear?
The plot should be linear with m=1.
What is the dissociation constant (Kd)?
The concentration of ligands that bind 50% of receptors in the absence of competing ligands.
What are the three ways K can be measured?
- Saturation (Ka)
- Competition (Ki)
- Schild analysis (Kb)
What does the slope of the Schild plot indicate if it is less than 1?
LogKb is over-estimated.
What does the slope of the Schild plot indicate if it is greater than 1?
LogKb is under-estimated.
What does the elimination process in Schild analysis involve?
Comparison of observed Kb and known Kb to eliminate subtypes not in response.
What does the summation process in Schild analysis involve?
Process of elimination to see which receptors are involved in agonist-induced response.
What does a slope greater than 1 in a Schild plot suggest about the antagonist?
- Toxic at high concentration
- Binding is irreversible
- Substrate of a saturate uptake system
What does a slope less than 1 in a Schild plot suggest about the antagonist?
The antagonist is allosteric.
