CB17: Receptors Flashcards
Define ligand.
A small molecule that binds to a specific receptor and initiates a response.
Define receptor.
A macromolecule that recognises a specific ligand and without the ligand, is silent.
What is juxtacrine signalling?
A signal transmitted for cells that are next to each other. Signal still touches the cell that secreted it.
What is autocrine signalling?
Signal is transmitted from one cell to itself.
What is endocrine signalling?
Signal is transmitted via blood.
What is paracrine signalling?
The signal is transmitted between cells that are next to each other but not touching.
How does the distance for the 4 types of signalling compare?
- Autocrine: short distance
- Juxtacrine: short distance
- Paracrine: µm-mm
- Endocrine: cm-m
What is a sub-type of paracrine signalling and what is the distance & response type for it?
Synaptic signalling.
Distance: 50nm
Response time: <1milisec
How does the response time for the 4 types of signalling compare?
- Autocrine: short
- Juxtacrine: short
- Paracrine: <1sec
- Endocrine: sec-min
Why are receptors located at the cell surface?
Most ligands can’t cross the plasma membrane due to being too big, polar or charged.
What are the 3 main categories of receptors?
- Ligand-gated ion channels,
- Enzyme-linked receptors,
- G-protein coupled receptors.
What kinds of molecules can have intracellular receptors?
Small, non-polar & uncharged molecules, like steroid hormones.
Define Kd.
The ligand concentration at which half of the receptors are bound.
What does Kd show ?
It shows a ligand’s affinity for a receptor.
If Kd is low what does this mean?
The ligand’s affinity for the receptor is high.
If Kd is high what does this mean?
The ligand’s affinity for the receptor is low.
What are the axis for the ligand-receptor binding curve?
- Y-axis: bound radiolabel
- X-axis: [ligand]
Define EC50.
The ligand concentration that produces half of the maximal response.
What does EC50 show?
A ligand’s potency.
If EC50 is low what does this mean?
The ligand is very potent.
If EC50 is high what does this mean?
The ligand is not very potent.
What are the axis for the dose-response curve?
- Y-axis: response
- X-axis: [ligand]
What are the units for Kd & EC50?
Units of concentration.
Define agonist.
A molecule whose binding activates the receptor & produces a response (the same as the one produced by the natural ligand).
Define antagonist.
A molecule whose binding does not activate the receptor or produce a response, but whose binding interferes with the natural binding of the ligand.
Differentiate between affinity and efficacy.
Affinity is the tendency of a ligand to bind to the receptor while efficacy is the ability of a ligand to produce a response.
What is a full agonist?
An agonist that will be able to achieve the maximal response.
What is a partial agonist?
An agonist that will not be able to achieve the maximal response.
What is a competitive antagonist?
An antagonist that binds to the same binding site as the ligand.
What is an irreversible competitive antagonist?
An antagonist that binds to the same binding site as the ligand but never leaves the binding site.
What is a non-competitive antagonist?
An antagonist that does not bind to the same binding site as the ligand.
State how the different antagonists can be overcome.
- Competitive antagonist: overcome by increasing [ligand].
- Irreversible competitive antagonist: not overcome.
- Non-competitive antagonist: not overcome by increasing [ligand].
Can maximal response be achieved with the different antagonists?
- Competitive antagonist: yes
- Irreversible competitive antagonist: no
- Non-competitive antagonist: no
How does the log[dose]-response curve look like with the different antagonists?
- Competitive antagonist: shape & size is same, curve is shifted right.
- Irreversible competitive antagonist: curve is shifted right & smaller.
- Non-competitive antagonist: curve is shifted right + shape changes.
How is maximal response achieved despite not all receptors being bound?
Due to a cell’s spare receptors.
What is up-regulation?
Increasing sensitivity to the ligand by increasing the number of receptors.
What is down-regulation?
Decreasing sensitivity to the ligand by decreasing the number of receptors.
