Lecture 16 Flashcards
What is the anatomy of G protein receptors?
A G protein receptor is a long chain of amino acids which goes in and out of the cellular membrane seven times. This is attached to the G protein found in the cytosol when activated (G protein is unactivated if not joined). and when unactivated it is unattached.
What are G protein receptors activated by and how does this relate to drug targeting?
They are activated by a diverse range of different ligands (e,g hormones, neurotransmitters, light). They are the largest class of cell surface receptors and hence represent the target of more than 50% of drugs in clinical use (but these drugs only target 10% of the G protein receptors in the body.)
How do G proteins work? What is their time scale?
G proteins will be unactivated until joined to the G protein receptor due to an agonist binding to the receptor, once activated by joining it will disjoin and then increase or decrease activity of an enzyme, changing the amount of second messengers (which will cause calcium release, protein phosphorylation and other effects). This alters the physiology/biochemistry of the cell and hence invokes a response. They can also interact with ligand and ion channels.
The time scale for this is seconds and an example of these is muscarinic ACh receptor.
Summarise G protein coupled receptors and ligand gated ion channels.
G protein: also called metabotropic receptors, located on the cell membrane, the effector is an enzyme or channel, coupling is done via G protein and the response time takes seconds (an example of this is the muscarinic ACh receptor).
Ion channels: Also called ionotropic receptors, located on cell membrane, effector is the channel, coupling is direct, response time is milliseconds and an example is nicotinic acetylcholine receptors.
What does dopamine activate and what is an associated disease and what is it characterised?
Dopamine activates dopamine receptor (G protein-coupled receptors), low levels result in parkinson’s disease (as the enzyme which produces second messengers important for movement is acting too much) and hence dopamine receptor agonists (like levodopa) are used to treat. It is characterized by a resting bremory, bradykinesia, rigidity and postural instability.
What is the problem with levodopa? Why is this a problem?
The problem with levodopa is that high levels of dopamine lead to psychosis (hallucinations and motor complications (dyskinesia). This wouldn’t be a problem if dosage could be kept low, but as the levodopa is used more are required.
How do antagonists act for G protein receptors? What is a commonly associated treatment and disease related to dopamine and what is a common problem with this treatment?
Antagonists work by binding to the receptor without activating the G protein. We use them in diseases which activate the receptors too heavily, a good example of this is antipsychotics, these act as an antagonist at sopamine receptors. This is used to treat psychosis.(commonly for schizophrenia). The problem is that this can induce parkinson’s disease like movements.
