Lecture 18 - Receptor agonists - inducing a response Flashcards
Ligand
something that binds- may be a natural ligand or a drug
Agonist
A ligand that binds to and activates a receptor
Agonists are ligands which activate different receptors. Name four types of receptor.
- ligand-gated ion channels
- G protein-couple receptors
- Kinase linked receptors
- nuclear receptors
The response that an agonists causes is measured through by two things…?
affinity and efficacy
What is affinity?
How well a drug binds to a receptor.
What is efficacy?
How well a drug activates a receptor
Responses are measured using concentration response curves. How would one of these curves be created? Draw one as an example.
- A biological system is exposed to increasing concentration of the agonist/drug
- The response is recorded- eg. cell growth, smooth muscle contraction
- The response (as a % of maximum) is plotted against log agonist concentration (M)
What does 1 in the graph show?
There is low initial concentration of the agonist so only a small response is produced- there is low receptor occupancy/ not many agonists are bound to receptors because of the low concentration.
What does 2 in the graph show?
The concentration of agonist increases so there is an increasing response.
What does 3 in the curve show?
The response will eventually max out when concentration of the agonist is very high. Why? Receptors are all occupied-full receptor occupancy. When they are all occupied, we will have our maximum biological response.
Define Emax. What does it measure?
The maximum effect produced by an agonist.
It measures how effective the agonist is at producing a response- efficacy.
The maximum effect that an agonist produces is not necessary equal to…
the maximum response of the biological system.
Where would Emax be in this curve?
What is EC50?
The concentration of the agonist required to produce only 50% of the maximal response. Basically concentration at half of Emax.
Where is EC50 in this curve?
Compare agonist A and B in terms of potency and efficacy.
- the agonist A and B have the same Emax but different E50 values.
- Agonist A has a lower E50 value than agonist B. Therefore, a higher concentration of agonist B is needed to produce the same response as agonist A, so agonist B is less potent than agonist A.
- Because they have the same Emax they have the same efficacy- both activate the receptor the same. But, they gave different EC50 values so they have different potencies.
Compare the Emax and EC50 of the two agonists- which is a full agonist and which is partial?
- Agonist A is a full agonist. Agonist C is a partial agonist, whose Emax is lower than Agonist A- has a lower maximum response.
- The Emax of agonist A is 100% so EC50 is taken at 50%
The Emax of agonist B is 50% so EC50 is taken at 25%
Describe how an inverse agonist works and draw the concentration response curve for them.
Biological systems and receptors have a base level of activity without an agonist present, such as heart muscle contraction. This activity is reduced by drugs called inverse agonists.
What is biased agonism?
Receptors can have more than one function. Different agonists may produce different effects on the same receptor. They promote different activation states of the receptor, activating different second messengers and therefore different responses.
The concentration-receptor curves are examples of what type of agonism? The blue and red lines represent… and the purple represents…
biased agonism
biased agonists
balanced agonist
