Topic 8: Drug Discovery Flashcards
(38 cards)
Why do ion channels make attractive drug targets?
many types, some are tissue selective allows for manipulation of electrochemical gradients
what drug binds to the SUR subunits of the K-ATP channels and causes closing?
Sulfonylureas and meglitinides
what is an inward rectifer
allows for the infux of ions more than its efflux
why are poly aminies more attracted to the pore when the membrane depolarises?
positivly charged so more attceted to pore ass depolarisation of the memebrane
What does ATP concentration and ADP concentration do to the open probability of Kir6
high atp closes low atp opens
ADP binding casues channel openig
What does ATP concentration and ADP concentration do to the open probability of Kir6
high atp closes low atp opens
ADP binding casues channel openig
what happens to membrane potenitail when k-ATP channels open
hyperpolarasation
what is the mechanism of stimulus secretion coupling in B cells
low glucose leads to less ATP and more ADP
ADP binds to K-ATP channels- opens
deplariation causes the cloisng og CA2+ channels
less ca2+ less secreation.
how does high glucose lead to insulin secretion
high glucose extrecellular
diffuseses - more metablism more ATP less
ADP
closingof K - ATP channels
depolation of the cell
opening of Ca2+ l type channels
simulation of secreation if insulin (vescicle binding)
What happens to insulin secretion when k ATP channels are inhibited?
no hyperpolariastion so more ca2+ opening and entry and hence moere insulin secreation.
what is permenat neonatal diabeties casuesed by ?
Kir6.2 Activating mutations
two forms mild and severe
mild is caused by a mutation to the ATP binding site - favours the open state
severe is caused by a gating mutation, increased open probbality - hyperpolarisation in many tissues.
what form of permanant neonatal diabeties will respond to sulfonylourea therapy?
mild
what causes congenital hyperinsulinism? what is it treated by?
mutaion in the SUR1 binding domain, causes the cahnnelto remain closed even in high ADP concentraion trated by channel openers such as diazoxide.
what are two 5-HT antagonists?
Alosetron and ondansetron
what part of the brain controls the vomit reflex?
the vomiting centre
what ligand is the nicotinic receptor superfamily sensitive to?
5-HT - cation selective excitatory receptors
what is the 5-HT 3 receptor coupled to?
Nothing it is an ion channel (ligand gated) the other 5-HT receptors are GPCRs
what is a Cys-loop receptor?
has a signature extracellular loop of 13 amino acids flanked by cysteines, which form covalent bonds
this loop forms a closed loop between the ligand binding domains and the channel domains.
what are the two ways the vomiting reflex can be activated?
chemoreceptor trigger zone and the GI tract
Where are the highest levels of 5-HT 3 receptors found?
in the vomiting centre and chemoreceptor trigger zone
why can the chemoreceptor zone detect chemicals in the blood?
it is not within the BBB
what can the chemoreceptor trigger zone be stimulated by?
toxins in the blood
higher brain centres
how does the chemorecepror trigger zone set off the vomiting reflex?
release of 5-HT, stimulates pathways to VC
vomiting
how does the GI tract stimulate vomiting?
enetrochromaffin cells are stimulated by luminal stimuli
release of 5-HT which stimulates peripheral 5-HT 3 receptors on vagal afferents, AP to brain stem
relase of 5-HT in brain stem - stimulation of VC
