01: Dose Response Relationship Flashcards
What are the 4 general classes of receptors
Ion Channel
G Protein
Tyrosine Kinase Receptors
Binding/Transportation to Nucleus (Chemotherapeutics)
What is the process that occurs after a drug binds a receptor and leads to a drug response?
Transduction
What type of receptor is a ligand-gated ion channel?
Ionotropic
What type of receptor links a drug to internal cell mechanisms through a G-Protein
Metabotropic
Which receptor type will make use of 2nd messengers like cAMP, AC, etc? (Ionotropic or Metabotropic)
Metabotropic
What is the general structure of an Ion channel receptor?
Protein pores in the plasma membrane
When a drug binds to an ion channel receptor it causes a conformational change, but what actually triggers a cellular response?
The change in ion concentration resulting from the ion channel opening (or closing)
What is the difference between an IPSP and an EPSP ion channel receptor?
IPSP = Inhibitory drug ligand
EPSP = Excitatory drug ligand
What type of sodium channels are cholenergic receptors?
Ligand-gated
What stimulus opens a voltage gated sodium receptor? (Hyperpolarization or Depolarization)
Membrane DEPOLARIZATION
What stimulates the opening of a cholenergic sodium channel receptor?
Acetylcholine (Ach)
What ligand is associated with Nicotinic ligand-gated channels?
Ach
What are the two types of Metabotropic receptors?
- activated alpha subunit (of G protein) binds and opens ion channel directly
- activated alpha subunit binds to a membrane enzyme, which activates a 2nd messenger to open ion channel.
What are 2 classic examples of the membrane enzyme that is activated by the alpha subunit in Metabotropic receptors?
Adenylyl Cyclase (AC) Phospholipase C
What is the second messenger that is activated by Adenylyl Cyclase in the Metabotropic transduction pathway?
cAMP
After cAMP is activated by AC, what is the next molecular messenger in the Metabotropic transduction pathway?
Protein Kinase A (PKA)
In the Phospholipase C transduction pathway what is the second messenger that PLC activates?
IP3
After IP3 is activated it travels to its target Calcium ion channel which is located on the membrane of which organelle?
ER
If cAMP and IP3 are second messengers, what are the first messengers?
The original signal molecules that bind to the G protein receptor (e.g. Epinephrine, Norepinephrine, etc.)
What is the polypeptide structure of a G Protein Receptor?
It is a single polypeptide in an alpha-helix configuration
How many times does each G Protein Receptor Polypeptide transverse the cell membrane
7
Which end of the GPCR polypeptide is on the cytosolic side of the membrane (NH3+ or COO-)?
COO-
G proteins are trimeric. What are the names of their 3 subunits?
Alpha
Beta/Gamma
When a G protein is in its rest state, what molecule is it bound to?
GDP
When a ligand activates a GPCR what happens to the GDP on the g protein?
It leaves and is replaced with GTP. The Alpha subunit dissociates from the Beta/Gamma
What must happen in order for the G protein to return to its resting state (bound to GDP)?
The extracellular ligand must dissociate from the GPCR
What molecule actually converts GTP to GDP when the G protein is returning to its resting state?
The G protein hydrolyzes its own GTP through the use of intrinsic hydrolytic functionality
What are the two sub-types of G protein that we will be dealing with in this course?
Gs (stimulatory)
Gi (inhibitory)
What G protein subtype is used in muscarinic GPCR’s
Gi
Why is the Gi protein considered inhibitory?
Because when Gi’s alpha subunit effects AC, it inhibits it.
What are RGS protein?
They are the proteins that “Reset” the G protein to its basal state
What is the effect of the alpha subunit of a Gs protein?
Increased activation of AC and increased cAMP
What is the effect of the alpha subunit of a Gi protein?
Inhibition of AC and decreased cAMP
What is the importance of Gi vs. Gs and their respective effects of intracellular cAMP levels?
Because that is the pharmaceutical effect (Mechanism of Action) of the GPCR related drugs that we will be studying in this course
What is the GPCR related consequence of Opiods?
Opiods activate Gi/ALPHAi thereby inhibiting cAMP production eventually leading to an analgesic effect.
The third most important subtype of G proteins is the Gq subtype….what is its effect?
Increased activation of PLC and increased levels of intracellular Ca++
A less common G protein subtype is Go, how does it work?
In a very similar fashion to Gi
What type of G protein would be associated with these pathway molecules:
PIP2, PLC, DAG, IP3, PKC
Gq
