Receptors Flashcards
What are class I nuclear receptors?
Lipophilic receptors that have to be recruited to the nuclear membrane
e.g steroid receptors
What are class II nuclear receptors?
Heterodimeric receptors already in the membrane which regulate transcription
Outline a GPCR response
- Agonist binding
- GDP detaches from the α-subunit and is replaced by GTP
- The α-subunit detaches from βγ and activates adenylyl cyclase which activates PKA which has downstream effects
- GTP is hydrolysed and βγ reattaches. This switches the signal off.
What type of structure has an NDMA receptor got?
Ionotropic glutamate type ion channel
What type of structure has GABAa and nAChR got?
Cys-loop type ion channel
What type of receptor is an insulin receptor?
Receptor tyrosine kinase
What class of receptor do cytokines activate?
Receptor tyrosine kinase
In myasthenia gravis, what sort of receptors do autoantibodies target?
Nicotinic acetylcholine receptors
Autoantibodies can lead to graves disease. What are the symptoms?
High metabolic rate
Increased skin temperature
Bulging eyes
Tachycardia (high heart rate)
What are overactive ligand gated ion channels in the brain associated with?
Epilepsy
Mutations in what class of receptors are usually associated with cancers?
Receptor tyrosine kinases
What are schild plots used to measure?
Reversible competitive antagonist affinity
Plots log[antagonist] against log[dose ratio -1]
What practical method is used to measure receptor affinity?
- Ligands are bound to the sample
- Unbound ligands are rinsed off
- Filter this to find percentage of bound ligands
When measuring ligands bound to binding sites, how are they incubated
Stored at low temperature and with antioxidants for stability
-ine molecules are oxidisable so must avoid air
What is drug efficacy?
How well a drug evokes a response
What is an intermediate efficacy?
If agonists occupy all receptors and cannot produce a full response. (Efficacy between 0 and 1)
How can cells become desensitised to drugs?
When a drug is given continuously,
Endocytosis of receptors and degradation. This leads to a loss of receptors.
Change in receptor e.g phosphorylation
Increased metabolic degradation
How many types of opiate receptor are there?
3
What type of opiate receptor do morphine and phentanol target?
μ-receptors
What are some side effects of opiate use?
Chronic constipation
Impaired breathing and brain functions
Name some μ-opiate receptor agonists
Morphine, heroin, methadone, codeine, fentanyl, β-endorphins
What sort of drug is naxolone?
μ-opiate receptor antagonist
What is a false substrate drug?
Drug which produces an abnormal metabolite or prevents transporters working
What is a prodrug?
Drug which binds an enzyme, releasing an active version of the drug
