Further Dug Targets Flashcards
What are GPCRs
They are receptors that sit in the cell mem, waiting for signals from the outside world and they interact with G proteins - cross the membrane several times aka they have seven transmembrane helices
What do GPCRS do?
- Several hundred devoted to smell
- Heart rate, speed and force of heart
- Relaxation of smooth muscle in lungs
- Eyes detecting light, light detected by gpcrs
What is sumatriptan
It’s the commercial name for imigran and is used in the treatment of migraine
What is cetirizine
Commercial name for zirtek and is used as a antihistamine
What does it mean when a G protein is described as heterotrimeric
This means that it is composed of 3 subunits.
α, β, γ
To which subunit does GDP bind to ?
α subunit
Describe the events leading up to GPCR activation
1) An agonist molecule binds to the receptor causing a conformational change
2) G protein itself also undergoes a conformational change where a exchange happens in the α subunit. The affinity for GDP is lowered whereas the affinity for GTP is increased - exchange of GDP to GTP- activating the G protein
What structure helps the Gprotein to attach to the cell membrane
Lipid molecules on the surface of the G protein adhere/embedd themselves into the membrane
What happens after the activation of the Gprotein
The gpG protein undergoes dissociation- dissociation from the receptor and Gα from the heterotrimeric structure, β,γ stay together. Gα then goes on to activate the “effector”. Once at the effector molecule Gα, there is some catalytic activity- cleavage of the GTP molecule to GDP and Pi- now the α subunit no longer wants interact with the effector molecule
At what point during the Gprotein cycle is the agonist released
Once the GTP molecule is hydrolysed back to GDP and Pi, the agonist molecule dissociates
Do GPCPR coupling target only ion channels
No enzymes aswell
What are the effector molecules of Gas?
The cAMP producing enzyme- adenylcyclase (converts ATP to CAMP)
What is the function of cAMP
It activates the protein kinase A which regulates the activity of a large number of enzymes
What does protein kinase A do
It increases the permeability of the cell membrane to Ca 2+ ions- Ca2+ channels open
To what receptor is the Gas subunit bound to
β-adrenoreceptor
What is the effector of the Gai/o protein?
Just like the Gas protein the effector molecule is the cAMP producing enzyme adrenylcyclase as well as potassium and calcium ion channels
What is the receptor that Gai/o binds to?
Opioid M2 muscarinic receptor- activated by Ach
What is the effect on the pottasium and calcium ion channels when activated by Gai/o?
The potassium channels allow a flux of K+ ions into the cells, aka the ion permeability increases whereas the permeability to Ca2+ decreases
What receptor does Gaq bind to?
M1 muscarinic receptor or α1 adrenergic receptor
What is the effector molecule of the Gαq protein?
Phospholipase C (PLC) which catalysts the breakdown of PIP2 into DAG and IP3