Receptors Flashcards
Define a Receptor.
Cellular receptors are proteins either inside a cell or on its surface which receive a signal from outside the cell and triggers an intracellular response.
Define a Ligand.
The ligand is a chemical messenger released by one cell to signal either itself or a different cell.
What are Second Messenger systems?
Intervene between the ligand (first messenger) and the ultimate intracellular response.
Take part in the cascade of events that transduces signal from the receptor-ligand complex into a specific intracellular response.
What is the classification for receptors?
- Cell-surface receptors/ Transmembrane receptors
- Internal Receptors
two types of internal receptors.
- Cytoplasmic receptors
- Nuclear receptors
Examples of Cytoplasmic Receptors
- Steroid hormone receptors (androgen, glucocorticoid, mineralocorticoid)
Examples of Nuclear Receptors
retinoic acid receptors, thyroid receptors
Classification of transmembrane Receptors (based on speed)
- Inotropic
- Metabotropic
- Enzyme-linked receptors
What are Inotropic receptors?
- ligand-gated ion channels
- Fast
- No 2nd messenger systems
What are Metabotropic receptors?
- e.g. G-protein coupled receptors
- coupled to 2nd messenger systems * Slow
What are enzyme-linked receptors?
- e.g. receptor tyrosine kinase(insulin receptor)
What is Receptor-Mediated Endocytosis?
- A special class of receptors is involved in the uptake of certain substances; e.g. Low-density lipoprotein (LDL).
- The receptor recognizes the LDL particle, binds to it, and mediates endocytosis.
- The signal is the LDL molecule, and the cellular response is endocytosis, hence second 2nd messenger systems are not involved.
Functions of a receptor?
- Recognition;
- Coupling;
- Signal transduction;
- Transport
What is the “Coupling” function of a receptor?
links recognition to signal transduction
Features of ligand-receptor interactions?
- Selectivity
- Affinity
- Efficacy
- Potency
What is the “selectivity” function of receptors?
the degree to which a ligand acts on a given receptor relative to other receptors (ligands can be selective or non-selective)
- e.g. cardio-selective; act on receptors on the heart only.
What is the “Affinity” function of receptors?
the extent to which a ligand binds to receptors at any given drug concentration
What is the “Efficacy” function of receptors?
the amount of physiological response a given ligand imparts for a given amount of receptor occupancy
What is the “Potency” function of receptors?
a measure of the amount of the ligand required to produce an effect of a given magnitude (influenced by both affinity and efficacy)
What are the four types of receptor “Efficacy”?
- (Full) Agonist
- Partial agonist
- Antagonist
- Inverse agonist
What does “Full Antagonist” Efficacy mean?
Examples?
Ligand that binds a receptor, producing a complete, intended response of the receptor.
salbutamol is a beta-2 receptor agonist
What does “Partial agonist” Efficacy mean?
Example?
Ligand that binds a receptor, producing a partial, intended response. (both agonistic and antagonistic effects)
domperidone is a dopamine receptor antagonist
What does “Antagonist” Efficacy mean?
Example?
Ligand that binds to a receptor, inhibiting/stoping the intended response of the receptor
aripiprazole has a partial agonistic effect on dopamine D2 receptors
What does “Inverse agonist” Efficacy mean?
Example?
Ligand that binds a receptor, producing the opposite biological response
H1-antihistamines. E.g. chlorpheniramine (Piriton)
What are the two main mechanisms for the regulation of receptor function?
- Regulation of receptor number
- Regulation of receptor activity/response
What is the expected outcome from receptor-linked regulation?
- Increase number/activity - upregulate
- Decrease number/activity - downregulate
How do you regulate receptor number?
Upregulation by synthesis
Downregulation by endocytosis/internalization
Downregulation by degradation
4 Examples of regulation of receptor number by Downregulation?
- uncoupling of receptors from second messenger systems (through phosphorylation) e.g. G-protein coupled receptor
- Arrestins
- Depletion of Secondary Messenger
- Depletion of downstream substances due to constant activation.
Example of regulation of receptor number by Upregulation?
Upregulation by the unmasking of receptors
