LC 38 Flashcards
Amplification
The process which involves a molecules binding to a receptor which uses secondary messengers to internally increase the effect of the one initial binding molecule
Second messenger
allow for multiplication, integration and modulation of the signal
adenylyl cyclase
Bound to by G protein and is responsible for activating cAMP using ATP
cAMP
cAMP is an example of a second messenger that responds to epinephrine and glucagon binding to create an amplified effect to activate the release of glucose
Protein Kinase A
Another example of a secondary messenger, is affected by cAMP
Examples of secondary messengers
G proteins, phosphatases, kinases, ion channels
Michaelis-Menten Equation
effect=Emax{ligand}/EC50+{ligand}
Emax
Max effects we can get out a system. Everything is bound and maximum potential has been met
EC50
concentration at which we get 50% the effect
Potency
Describing the interaction/binding strength of ligand to a receptor. How much drug is needed to get maximal effect? Moves to the left on the graph is more potent, versus moving to the right which is less potent
Semi-log plot
The most common method for displaying ligand-receptor interactions. S curves displaying efficacious and potency to compare ligands
Math
Describing the magnitude of the effect of a ligand/receptor
Efficacy
Describing the activation of a receptor by a ligand. Increase the Emax.
Higher the effect = _____ efficacious, lower effect = _____ efficacious
more, less. Moving upward on the graph is more efficacious versus moving down on the graph.
____ drug = more potent, ____ drug = less potent
less, more
Full agonist
a ligand that binds to the receptor and activates maximal response equal to endogenous ligand
Emax=Emax
partial agonist
a ligand that binds to the receptor and activates less than maximal response.
Emax is less than endogenous Emax
super agonist
A ligand that binds to the receptor and causes a response greater than endogenous full agonist
inverse agonist
a ligand that binds to the receptor and causes the opposite effect of an agonist –> receptors that have basal signaling activity with no agonist
antagonist competitive
ligand “blank” that prevents the actual ligand from entering and binding. No change induced
antagonist non-competitive
doesn’t bind at binding site but still prevents reaction from proceeding –> binds at allosteric site
reversible antagonist
measurable Koff
irreversible antagonist
no measureable Koff –> covalently bound
looks like a non-competitive antagonist because the agonist cannot compete for binding
modification
Describe how a signal is modified by agonist or antagonist
agonist
binds to produce signaling effect and can be measured in potency and efficacy
Antagonist
prevents receptor activation.
Example of a super agonist
goserelin used to downregulate sex hormone production in breast and prostate cancer
Example of inverse antagonist
Ro15-4513 to counteract alcohol poisoning
examples of u-opiod receptor acting drugs
morphine, buprenorphine, goserlin, Ro15-4513
example of partial agonist
buprenorphine - can act as antagonist against more efficacious agonist
Competitive antagonists can be overcome by increasing the concentration of signaling ligand
- does not kick out antagonist but does compete with antagonist for binding sites
- ability to overcome is partially dependent on K1 of antagonist
Example of competitive antagonist
naloxone (competitive for opioid receptors)
Example of non-competitive antagonist
ketamine
K off
-rates can differ in speed
Practically irreversible
the K off rate of the antagonist is so low physiological functions cannot occur - residence times in seconds to minutes range
