JC1: Signalling, receptors, and pharmacology (1) Flashcards
What is Paul Ehrlich’s famous quote about receptors (include the modification)?
“A drug will not work unless it is specifically bound”
What is the scientific name for aspirin?
Acetylsalicylic acid
What is the molecular mechanism of action of aspirin?
Irreversible inhibition of cyclooxygenase (COX)
What are the four properties of aspirin?
- Anti-inflammatory
- Antipyretic
- Analgesic
- Antiplatelet
What are the four types of receptor (superfamily of proteins)? Give an example for each.
- Ligand-gated ion channels, e.g. nicotinic acetylcholine receptor
- Receptors with intrinsic enzymatic activity, e.g. insulin receptor
- G protein-coupled receptors, e.g. β-adrenoceptor
- Intracellular (nuclear) receptors, e.g. glucocorticoid receptors
What is the substrate for the enzyme cyclooxygenase?
Arachidonic acid
What are the substrates of adrenoceptors?
Adrenaline and noradrenaline
What are endogenous ligands?
Ligands the body produces naturally
What might exogenous ligands be?
Natural compounds (e.g. plant secondary metabolites) or laboratory-synthesised ligands
What is an alternative name for adrenoceptors?
Adrenergic receptors
What is the difference between noradrenaline and adrenaline?
Adrenaline has a methyl group at the end of the chain, whereas noradrenaline doesn’t
What is a competitive inhibitor of adrenaline?
Propranolol
What is the US name for isoprenaline?
Isoproterenol
What is the US name for adrenaline/noradrenaline?
Epinephrine/norepinephrine
What is the US name for salbutamol?
Albutertol
How many times does a G protein-coupled receptor cross the lipid bilayer?
Seven times
By what is ligand binding governed?
Kinetics of association and dissociation
By what is ligand affinity governed?
Association vs. dissociation rate
What is the law of mass action?
L + R ⇌ LR
(ligand + receptor ⇌ ligand-receptor complex)
What is EC50?
The effective concentration of ligand producing 50% of Emax (maximal response)
What is potency?
ligand affinity + ability to cause a response
What defines the ligand-receptor interaction?
Affinity and efficacy
What is efficacy?
The ability to produce a desired or intended result
How can radioligand binding be used to quantify the ligand-receptor affinity?
A radioactive form of the agonist or antagonist ligand is allowed to bind to cells (or membranes prepared from cells)
Low ligand concentration = low binding affinity
High ligand concentration = high binding affinity
What is the downside of radioligand binding?
It gives no information on what happens subsequent to binding, i.e. whether the ligand possesses intrinisc efficacy
Do agonists possess affinity for the receptor and intrinsic efficacy?
Yes
Do antagonists possess affinity for the receptor and intrinsic efficacy?
No; they only posses affinity for the receptor
What is intrinsic efficacy?
The ability to cause receptor activation
What is the effect on the concentration-response curve of a competitive antagonist?
It shifts it to the right
