Receptors and the effects of drugs Flashcards
Describe the patch clamp technique
How is it different to whole cell recording?
A method of looking at responses generated by individual receptors
Electrodes contact membrane and create electrical seal, any changes are due to receptors.
In whole cell recording the size of responses vary
Describe response and graph for:
- full, high efficacy agonist
- partial, low efficacy agonist
- no agonist (or antagonist)
- inverse agonist
- sigmoidal curve, reaches saturation, maximal response
- sigmoidal curve, reaches saturation, doesn’t reach maximal response
- no response, straight line, constitutive activity still detected, functional in absence of agonist
- opposite to agonist, inhibits spontaneous activity, graph falls
An example of an allosteric affect on receptor is benzodiazepine receptors and GABAa receptors. Describe normal function and effect of drug
Example agonist…
GABAa - GABA binds to to chloride channel, Cl- enter cell, hyper polarisation, inhibits AP
Benzodiazepine receptor - drug binds to allosteric site, conformational change, increases affinity of GABA and so increases channel opening
Effect = reduces epileptic seizures
e.g. diazepam
5 types of antagonist
- competitive
- irreversible
- allosteric
- channel blockers
- “physiological antagonists”
Competitive antagonists
- example
- effect on response curve
- atropine in nicotinic ACh receptors, compete with agonist for binding site, reversible
- shifts curve right,
Explain how partial agonists can behave as competitive antagonists
Partial agonist does not produce full response. If you put a high conc of partial agonist, put a full agonist in, partial agonists act as an antagonist
Irreversible Antagonist
- what is it?
- effect on response curve
- why can you still get maximal response at low cons of antagonist
- compete for same binding site but antagonist binds irreversibly
- shifts to the right and maximal response decreases
- receptor reserves
Allosteric Antagonist
- examples x2
- what do they do
- gallamine at muscarinic receptor, betacarbolines at the GABAa receptor
- bind at distinct site from the agonist and decrease agonist affinity
Channel blockers
- where do they act
- what do they do
- what is meant by use-dependence
- ligand gated ion channels
- Bind inside the channel and prevent the passage of ions
- binding of channel blockers tends to be enhanced by receptor activation (more likely to bind if the channels are open).
“physiological antagonists”
what are they?
- an agonist offsetting the response of another agonist
- produces opposite effect on tissue
What is desensitization?
Prolonged or repeated exposure to an agonist reduces the response to that drug
