NT-synthesis I - Salmen Flashcards
is the response to a drug always the same (i.e. should one always activate 50% of the receptors?) how could this be monitored?
No. one may not need to activate 50% of the receptors to get max response (affinity is not the same as efficacy). Therefore, the biological readouts are very important in drug testing (I.e. physiological/phenotypical responses to the drug- e.g. elevation of the tail in rodents in response to opiates) receptor subtypes are also important for the potency of a drug.
what is the difference between reversible and irreversible antagonist? (+ description of curve)
- Reversible antagonist competes with the agonist on the receptor, and will make it harder for the agonist to bind to the receptor so it will take longer to reach max. response. however, once the antagonist is not bound, the receptor can bind to the agonist without change in response. the curve will have the same shape but the position will be shifted to the right on the X axis (i.e. more drug needed to reach max response).
- Irreversible antagonist- Increasing concentration of the irr. antagonist will decrease the efficacy of the agonist–> the response (max) level will decrease because these antagonists affect the receptor structure so agonist can’t bind. the curve thus will change its slope and become flatter.
what is the role of tyrosine kinase in receptor activation, and what factors affect its activity?
receptor with Tyrosine kinase co-receptor phosphorylate the other receptor. This phosphorylation can only occur at a certain distance –> phosphorylation increases at optimal distance e and decreases the further apart the receptors are from each other.
which statement(s) is/are correct?
a. reversible antagonists do not affect the distance of the receptor and the tyrosine kinase receptor so phosphorylation rate doesn’t change.
b. reversible antagonists keep the 2 receptors at a long distance so phosphorylation rate is lower
c. inverse agonist decreases the receptor activity, because it keeps the receptors at a long distance from each other (decreases activity of R even if its ligand free since distance is the key factor)
d. with a reversible antagonist the agonist concentration needs to be higher.
e. inverse agonist + antagonist will keep the receptor more active than only inverse agonist
a, c, d, e
what was the ‘Vagusstoff’ experiment?, what did it prove?
- Vagusstoff experiment was an experiment done by Otto Löwi that discovered the existence of NT- ACh in the Vagus nerve.
steps: A. in donor heart: 1. stimulate the Vagus 2. heart rate goes down 3. take fluid sample
B. in recipient heart:
- add fluid sample from donor
- heart rate goes down!
–> the process was reversible - went back to normal after washing of the sample
primary definition of NT
def: a substance released by a nerve ending, used to communicate with different adjacent neurons. NT is released from the presynaptic neuron and excite/inhibit the postsynaptic neuron. It is quickly dgraded in the synaptic cleft or taken up by the releasing neuron.
what are the problems with the primary definition of NT?
problems:
1. not all NTs are released from pre to postsynaptic neuron (there are retrograde messengers, presynaptic autoreceptors etc.)
- Ion channels vs. metabotropic cascades- nACh - mACh; iGluR - mGluR; GABAaR - GABAbR
- limited extracellular lifetime (quick degradation)- tonic substances- concentration
which of the statements about Disulfarim is WRONG?
a. Disulfarim inhibits alcohol dehydrogenase
b. disulfarim increases levels of Acetaldehyde in the liver–> bad hangover symptoms
c. Dusulfarim inhibits activity of aldehyde oxidase
d. disulfarim stays active in the body for 2 weeks
e. under the influence of disulfarim, hangover symptoms occur 10 min after alcohol intake
c
how does pharmacokinetics affect the addiction potential of drugs?
Drugs that are delivered and distributed very fast are highly addictive–> the drugs are more potent and elicit a response without activating 50% of the receptors.
what are the orders of biomolecules?
A. low order BM- sugars, peptides, ketogenic compounds
B. Medium order BMs-
- can contain low order BMs
- peptides: opiates
- nucleotides: ATP, GTP, NADPH, DNA/RNA bases
C. High order BMs-
- can contain medium order BMs
- large polymeric molecules
- proteins, DNA/RNA
which of the following statements about sugars is WRONG?
a. sugars exist in cis and trans form
b. some sugars are non-polar so there is no need for hydration envelope
c. sugar metabolism is happening in the following order: sugar + p –> glucose –> pyruvate –> acetyl CoA
d. sugars can be converted into fats but fats cannot be converted into sugars.
b
True or false:
Neurotransmission in the purinergic synapse involves both classical fast ionotropic transmission AND metabotropic transmission which activated various signal cascades
true
describe the processes in the purinergic receptors
- ATP and ApnA colocalise w. other NTs
- ATP activates P2Y and P2X
- a. P2Y: couples mostly go to Gqu–> PLC and PI pathways
- b. P2X: excitatory inotropic receptor
- ATP degenerated by- Ectodisphosphohydrolase and Ecto-5’-nucleotidase to ADENOSINE
- Adenosine can activate the P receptors A1 & A2 –> stimulations./inhib. cAMP
- many transporters–> N1 is Na+ dependent
characteristics of lipids and fatty acids
- No need for hydration envelope with one acidic pole and one basic pole.
- Main component of the lipid bilayer
- can build lipid rafts
what are lipid rafts?
- Cholesterol rich patches of membrane forming a distinctive microenvironment.
- many receptors cluster around them so they can dimerise faster–> so a signal transduction can occur faster.
- often rafts are attached to molecules and anchor them to membrane
- important for post synaptic structures
