regulatory, enzymes, transport, and structural
What are our 4 types of drug receptors?
nuclear, rtk, cytokine, ion channel, gpcrs
What are our 5 types of regulatory receptors?
Nuclear receptor
-primarily responds to lipid-soluble drugs
-drugs can cross cell membrane and act via intracellular receptors
activating gene expression
What is the most common downstream mechanism for Nuclear receptors?
several
A typical nuclear receptor is composed of ______ domains
Nuclear
What receptor class do these receptors fall under: glucocorticoid, estrogen, androgen, thyroid hormone?
RTKs
-receptors are transmembrane proteins with extracellular ligand binding domains and intracellular enzyme domains
ligand binds ec domain; conformational change; units dimerize, kinase domains come together
How does signaling event work in RTKs?
Dimerization
The chemical reaction that joins two molecular subunits, resulting in the formation of a single dimer
ligand or cell type
Dimerization partners are dependent on ______ or _______
Cytokine receptors
-large class of molecules
-pass signaling event from extra- to intra-cellular
cytokine
Which form of regulatory receptor possess signaling mechanisms extracellular & intracellularly?
Ligand-gated ion channels
ligand binds receptor---> opens channel, ions flux down electrochemical gradients
multiple subunits
Ligand-gated & Voltage-gated are both composed of what ?
endogenous ligands
How are ligand-gated ion channels categorized?
ions, speed of activation/inactivation, direction of ion flow
How are voltage-gated ion channels categorized?
endogenous ligand receptors
GABA-A, ACh- nAChR, and NMDA-R are what kind of receptors?
resting, open, desensitized
what are the three stages of signaling in ligand-gated ion channels?
resting
- channel is closed and ready to activate when ligand binds
open
-ions are allowed to pass through the cell membrane
desensitized
-no longer passing ions but not ready to activate again-not "sensitive" to ligand
modify the orthosteric site to alter transition from rest to active, block open channels, allosterically modulate desensitization
How can we modulate the three states of ligand-gated ion channels?
force resting channels open/closed, block open channels, modulate inactivation, modulating subunits
How can we modify voltage-gated ion channels?
GPCR
-most complicated of the coupling systems
-leads to great signal amplification
GPCR
Which regulatory receptor consists of signal transduction or pathways/cascades?
ec ligand binds to specific R, G-protein gets activated on cytoplasmic/intracellular surface, G-protein changes activity of some effector
How do GPCRs work?
G-proteins
-family of proteins that function as molecular switch, an intermediate in R-E coupling
heterotrimeric & small g proteins
_______ & ________ are two types of G-proteins
by the secondary activity on their effectors
How can we further divide G-proteins?
cAMP
-most famous/common intracellular 2nd messenger
-mediates hormal responses, renal water conservation, calcium homeostasis, etc
adenyly
How is cAMP activated?
cGMP
-only active in a few cell types, i.e. intestinal mucosa and vascular smooth muscle
-similar activity to cAMP
guanylate cyclase
How are cGMPs activated?
effects begin high, diminish over time
Explain GPCR signaling dynamics.
ATP, substrate, and co-factor
What do enzymes require to signal?
inhibitors
what are most enzyme - targeting drugs characterized as ?
structural proteins
-critical for mechanical support and cellular movement
-drug targets include tubulin