Receptor theory Flashcards
Sir Henry Hallet Dale
-1875-1968
-pharmacologist + physiologist
-discovered acetylcholine
James Black
-discovered H2 antagonist, cimetidine (suppresses the formation of gastric acid and is used to fight ulcers)
-nobel prize in 1998
Old waiting chair occupancy model
-developed by A.J Clark
Chair analogy
-chairs= receptors
-people= agonist
-people sit and get off of chairs completely randomly, such as agonists bind and unbind randomly
-1 to 1 exchange, 1 agonist occupies 1 receptor to illicit 1 response
-the more receptors that are occupied, the more response
-MAXIMUM RESPONSE is when all receptors are occupied
A. J Clark
provided the first quantitative study of antagonism of acetylcholine by atropine
Agonist
-usually something in your body
-a drug or a molecule or ligand etc that binds to a receptor to produce a response
Exogenous molecules (agonist)
try to mimic that natural endogenous molecule
-produces the intended response
Antagonist
(safer term to use is inhibitor, unless exact mechanism is known)
-a drug or molecule or ligand etc, that binds to a receptor to interfere with an agonists response
-can either stop the response or lessen the response
Dose
concentration of drug (molecule), usually measured in moles
Response
The observable change associated with variation in agonist concentration: can be contraction, secretion, inhibition, etc
Effect
synonymous with response: drug effect produces response
Log(agonist)
useful measurement tool because very large magnitude differences in concentrations can be represented on the X-axis with small, simple numbers
%inhibition
A type of response whereby the thing being measured is how much an effect that would usually be present is inhibited in the presence of an agonist
Potency
The strength needed for a drug to elicit a response
Eg; the MORE potent the drug the LESS of it is needed to create a response
Efficacy
-The response of a drug
-the maximum response of a drug means that even with an increase of the drug, the response cannot decrease
Eg; “doability” the more efficacious, the more drug can DO its job and get a RESPONSE
Affinity
How attracted the drug and receptor are to each other
Eg; “stickability” the more affinity, the greater they can stick together
EC50
A quantitative measure that indicates how much (concentration) of a substance (e.g. drug) is needed to produce, in vitro, 50% of the maximal response
kD
Can be extrapolated from EC50- big pharmacological importance
kD= kON/kOFF
IC50
A quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, in vitro, a response by 50%.
(would be an antagonist)
TDLR EC50
The concentration of the drug needed to produce 50% of its maximum response.
Competitive antagonism
-There is only a shift to the RIGHT and NO change in maximum response
-with this type of antagonism, you can still get back to the maximum response with an increase in the agonist (drug)
(CAUTION: it is hard to prove - you need to know the exact mechanism that causes this shift. If you want to argue it is a competitive antagonist use surmountable antagonist)
Irreversible antagonism
-There is a DOWNWARDS shift and a CHANGE in MAXIMUM RESPONSE
-with this type of antagonism, with the same dose of agonist, or increase in agonist, you can NO LONGER achieve the same maximum response. Thus, its IRREVERSIBLE
(CAUTION: it’s hard to prove, you need to know the exact mechanism causes this shift. So if you want to argue it without saying it, use INSURMOUNTABLE antagonism - COVALENTLY BONDED)
Daniel Bovet
Discovered H1 antagonist and won noble prize in 1957
Stochastic nature of the body
-it is completely random which molecule binds to which receptor
-at any moment there will be a population of binding sites
-which sites are bound will depend on the number of molecules that preferentially bind to that site
-if the molecule has diffused away from that site it becomes available for other molecules - similar (agonist) or dissimilar (antagonist) to bind to the previous receptor
Equilibrium
forward reaction = the reverse reaction
kON = kOFF
When the rate of forming a new signal-receptor complex= the rate at which an existing signal-receptor complex dissociates
kON
how fast a molecule gets to receptor
kOFF
how long the molecules stay on receptors
neurotransmitters
-high kD (fast off rates)
-low affinity
hormones
-low kD (slow off rates)
-HIGH affinity
The law of mass action
IT’S JUST EQUILIBRIUM
Four categories of membrane receptors
-receptor channel
-G protein-coupled receptor
-receptor-enzyme
-integrin-receptor
Catalytic receptor
-receptor-enzyme
-integrin-receptor
Receptor channel
Ligand binding opens or closes the channel
G protein-coupled receptor
Ligand binding to a G protein-coupled receptor opens an ion channel or alters enzyme activity
Receptor-enzyme
Ligand binding to a receptor-enzyme activates an intracellular enzyme
Integrin receptor
Ligand binding to the intern receptors alters enzymes or the cytoskeleton
Signal transduction pathways
Mast Zellen
swollen or fat; coined by Paul Ehrlich
Ubiquitous
everywhere (mast cells are ubiquitous in the body)
Organ bath
Ex vivo, measures force transacted by tissue sample
Example: testing how much a sample of intestinal tissue contracts or relaxes in the presence of loperamide (Immodium)
Ussing chamber
Ex vivo, measures molecule movement across a membrane
Example: testing how much acid a sample of epithelial parietal tissue secretes in the presence of histamine
SEM microscope
Gives 3 dimensional images of lower resolution
TEM microscope
Gives 2 dimensional images of higher resolution
Southern blot identifies
DNA
Northern blot identifies
RNA
