Exam 1: Receptor Theory Flashcards
3 factors in receptor concept
- Receptor affinity determines dose (Kd)
- Receptor selectivity varies per drug
- Receptors can be activated (agonist) or blocked (antagonist)
Orphan Receptors
No known endogenous ligand
Applies to roughly 50% of all GCPRs
Catagorizing receptors by molecular structure
- 7TM receptors (GPCRs)
- Ligand gated channels
- ion channels
- catalytic receptors
Cell signalling process
- Signaling molecule (drug or ligand)
- Receptor
- Signal transduction proteins (second messengers)
- Second messengers (cAMP, DAG, IP3
- Effector protein (elicit response)
4 Transmembrane signaling methods
- Intracellular receptors (lipid soluble, uncharged)
- Catalytic (activates enzyme on inside of cell)
- GPCRs (G-protein is used during activation to activate an enzyme and elicit a response)
- Ion channels (allow Na, K, Ca, etc… throught the membrane down concentration gradient)
GCPR utilizes a
G-protein which is activated by GTP. G-protein then attaches to effector protein
G-proteins structure
Trimeric
- Alpha
- Beta
- Gamma subunits
- GDP –> GTP (active)
Drugs related to Gene Expression
Lag period
- may take hours to see response as transcription/translation takes longer
Persistence
- response could remaine for hours or days until protein pathways degrade
GCPR structure
7-TM spanning domains
has amino terminal end (outside) and carboxy terminal end (Inside)
Many downstream effects possible with:
GCPRs
GCPR response time
Fast - if activating an ion channel
Slow - if activating a transcription pathway
The 2 most important 2nd messengers are
cAMP (most common)
IP3
most important Catalytic Receptor
Tyrosine Kinase (RTKs)
RTK process
ligand binding stimulates
- Dimerization (two monomers binding together)
- phosphorylation of tyrosine residues
- activation of docking sites
Ion channels can be:
Voltage gated channels
Ligand gated channels
