1.4 receptor Flashcards
(30 cards)
What is a key pharmacologists aim to regarding receptors?
What receptors are present in cell X and what is their function?
Why is identifying receptor subtypes important?
To develop selective drugs that reduce side effects by targeting specific receptor subtypes.
Which receptor family is used as an example in this lecture?
Muscarinic cholinoceptors (mAchRs), subtypes M1–M5.
What effect does acetylcholine have on airway smooth muscle (ASM) cells?
It binds mAchRs and causes ASM contraction, narrowing airways and increasing Ca²⁺ levels.
What is the goal of saturation binding studies?
To determine the affinity (KA) of the radioligand and the total receptor number (RT).
What radioligand is commonly used in mAchR studies?
[³H]-QNB, which binds to all mAchR subtypes with similar affinity.
Can saturation binding studies identify specific receptor subtypes?
No, they measure total receptors but do not differentiate subtypes.
What does a competition binding study involve?
Increasing concentrations of a selective unlabeled ligand competing with a fixed [³H]-QNB for receptor binding.
What can competition binding studies reveal?
The affinity of ligands for receptors and the subtype proportions present.
What does IC₅₀ represent?
The concentration of competitor ligand required to displace 50% of radioligand binding.
Why isn’t IC₅₀ a direct measure of affinity?
Because it depends on the concentration of the radioligand used.
Which equation is used to calculate Ki from IC₅₀?
The Cheng-Prusoff equation: Ki = IC₅₀ / (1 + [D]/Kd).
What does pKi represent?
The negative logarithm of the Ki value (–log Ki), indicating ligand affinity.
What does a high pKi value indicate?
High binding affinity of the ligand for the receptor.
If Ligand A has a pKi of 8.0 and matches known M3 values, what does this suggest?
The cell preparation likely contains a pure population of M3 receptors.
What does a steep sigmoidal competition binding curve suggest?
A pure receptor population or a mixture where the ligand has equal affinity.
What does a biphasic binding curve indicate?
Presence of two receptor subtypes with significantly different ligand affinities.
What can be inferred from the point of inflection (POI) in a biphasic curve?
The relative proportions of high- and low-affinity receptors.
What does a shallow sigmoidal curve suggest?
A mixture of receptors with slightly different ligand affinities.
Why can’t shallow curves be interpreted by eye?
Because they reflect subtle binding differences; require model fitting and computational analysis.
If Ligand A has different pKi values for each mAchR subtype, what does this indicate?
It is selective for all subtypes and can help identify subtype composition.
If a steep curve for Ligand B gives a pKi of 9.0 and matches M3, what does that suggest?
The receptors are likely a pure population of M3 receptors.
If Ligand B’s pKi is 7.0 and the curve is steep, what is likely?
The population may include M1, M2, M4, and/or M5 receptors (equal affinity), but not M3.
What does a saturation binding study determine?
KA of the radioligand and RT (total receptor number).
