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
How can toxicity of heavy metals be reduced with chemical antagonism?
Using chelating agents, e.g dimercaprol
Outline chemical antagonism
Substances reacting in solution, so that effects of the active drug are lost
Outline non-competitive antagonism
Blocks a step between receptor activation and response
Does not compete with the agonist
Inhibits function of a signalling molecule
Outline pharmacokinetic antagonism?
Change in drug metabolism, e.g decreasing absorption in the GI tract
Warfarin thins blood, reducing a drug’s effective concentration in the bloodstream
Change in excretion of an agonist
Drugs that alter protein binding and filtration
What is physiological antagonism?
Two drugs with opposing actions in the body interacting
Endogenous mediators- describe actions through separate cells or transduction-receptor systems
Outline competitive antagonism
Compete with agonists for a receptor
The complex formed does not stimulate any downstream effects
What is dose ratio?
How many more times an agonist is required in the presence of an antagonist
How do irreversible competitive antagonists come about?
Bond created between the drug and receptor. This antagonism cannot be reversed by washing.
e.g dibenamine blocking histamine responses.
Give the definition of a drug
chemical of known structure which produces a biological effect in living organisms
Give the definition of a receptor
protein which recognises and binds chemical mediators
What is a medicine
preparation which contains a drug to produce a theraputic effect. Often contain excipients, stabilisers and solvents
How can the molecular nature of a signal transduction mechanism be predicted?
Class/structure of the receptor
Give 3 examples of chemical mediators
Hormones
Neurotransmitters
Antibodies
What are first generation biopharmaceuticals?
endogenous proteins produced with DNA technology
What are second generation biopharmaceuticals?
engineered proteins to improve performance
What is -mab the suffix of?
monoclonal antibody
What is -asone the suffix of?
corticosteroid
What is -caine the suffix of?
local anaestetic
What is -statin the suffix of?
lipid lowering drug
What is -artan the suffix of?
angiotensin receptor blocker
What is -dipine the suffix of?
calcium channel blocker
What is -barpital the suffix of?
barbiturate
What is EC50?
Effective concentration of a drug which gives 50% of a maximal response
What is a receptor reserve?
less than 100% of receptors have to be occupied to give a max response
