1.2 Receptors Flashcards
(15 cards)
What are receptors and what is their role in cells?
Receptors are the cell’s sensing elements that recognize endogenous hormones, neurotransmitters, and mediators. They transduce binding signals into changes in cell activity.
What is an agonist, and what two key properties does it possess?
Answer:
An agonist is a ligand that activates receptors. It possesses:
Affinity: The tendency to bind to a receptor.
Efficacy: The ability to activate the receptor once bound.
How do full agonists and partial agonists differ?
Full agonists: High efficacy, producing maximal receptor activation and large cellular effects.
Partial agonists: Lower efficacy, producing submaximal activation and smaller effects.
What determines the magnitude of agonist-induced cellular effects?
Drug-dependent factors: Concentration, affinity, and efficacy.
Cell-dependent factors: Receptor density (RT) and coupling efficiency (f) of signalling pathways
What is the EC50 value, and what does it measure?
The EC50 is the agonist concentration producing 50% of its maximal response. It measures agonist potency, which depends on affinity, efficacy, RT, and f.
How does receptor density (RT) influence agonist effects?
Higher RT increases cellular response (e.g., more receptors = larger effect). Reduced RT (e.g., in disease or by irreversible antagonists) diminishes response.
What is biased agonism, and what is its potential benefit?
Biased agonism: An agonist selectively activates specific signalling pathways of a receptor (e.g., G protein vs. β-arrestin).
Benefit: Separation of therapeutic effects (e.g., analgesia) from adverse effects (e.g., respiratory depression).
What are the three types of biased signalling?
Ligand bias: Unique ligand-induced receptor conformation.
Receptor bias: Receptor modifications (e.g., mutations, splicing).
System bias: Differential effector expression in cells.
How does coupling efficiency (f) affect agonist response?
Cells with high f (efficient signalling pathways) produce larger responses for the same receptor activation level (e.g., overexpressing adenylate cyclase amplifies xamoterol’s effect).
What is the traditional vs. modern view of receptor signalling?
Traditional: 1 receptor → 1 linear pathway (e.g., GPCR → G protein → effector).
Modern: Receptors are “promiscuous,” activating multiple pathways (e.g., G proteins, β-arrestin) depending on the agonist.
Give an example of biased agonism in clinical use.
TRV130 (Oliceridine) is a μ-opioid receptor agonist that preferentially activates G protein pathways (analgesia) over β-arrestin pathways (reducing side effects like respiratory depression).
What is the relationship between efficacy and effectiveness?
Efficacy: Ability to activate a receptor (only agonists have this).
Effectiveness: Ability to produce a clinical response (both agonists and antagonists can be effective).
How does the dose-response curve relate to agonist potency?
A sigmoidal dose-response curve plots agonist concentration vs. effect. The EC50 (midpoint) indicates potency; lower EC50 = higher potency.
What happens when a biased agonist binds to a receptor?
It stabilizes a unique receptor conformation, selectively activating certain pathways (e.g., G protein but not β-arrestin), leading to distinct cellular effects.
Why might two cell types respond differently to the same agonist?
Differences in receptor density (RT) or coupling efficiency (f) alter signal transduction magnitude, even for identical receptor activation levels.
