Neuro-Drug Targets Flashcards
What are the major five classes of drug targets
1) Membrane receptors
2) Nuclear receptors
3) Ion Channels
4) Transport Proteins
5) Enzymes
What is the very basic order of membrane receptors signal transduction
1) Ligand binds
2) Membrane receptors are bound
3) Intracellular signaling intermediates
4) Cellular response
What is the most common membrane protein drug target
GCPR
What is the target of dobutamine
B1 agonist
What is the process of down-regulation in GCPRs
When a true triggers activity in the G protein, it will illicit the result, however over time, as the drug remains, the effect will become desensitized
What the result of a patient on Beta blockers over time that suddenly stops
The presence of a beta bloacker will lead to the up regulation of the B2 receptor, but the beta blocker will keep from ever seeing a result. If the patient suddenly stops, they become very sensitive to NE with devastating responses
What must all transcription factors contain
DNA binding segment
Where do transcription factors usually bind
Promoters or enhancing regions that are adjacent to the coding region of the regulated gene
What is the specific region that a transcription factor will bind to
Response elements
What usually occurs at the N-terminal of the GCPR
Glycosylated
Where is the N terminal located in the GCPR
Extracellular portion
Where is the C terminal of the GCPR located
Cytosol
What usually occurs at the C terminal of GCPR
Phosphorylated at serine/threonine sites)
What portion of the GCPR contains the G protein binding sites
Cytoplasmic loops
Which region of the GCPR usually interacts with cytoplasmic regions upon ligand binding
Third cytoplasmic loop connecting regions 5 and 6
What is the event with GCPR that can lead to receptor endocytosis
Phosphorylation of the terminal serine and threonine hydroxyl sites
What is the process of ligand binding causing the activation of the GCPR
1) Ligand binds and activates the heterotrimeric G protein by the receptor
2) GDP is released and GTP is able to bind
3) GTP bound state is able to activated enzymes/channel
4) GTP is cleaved to GDP in order to deactivate the GCPR
The Gs family of GCPR activates which enzymes
All adenyl Cyclase and Src Tyrosine kinases
What group of enzymes are affected by the Gi family of GCPR
Inhibition of adenylyl cyclase, but will activate Src tyrosine kinase
What enzymes are affected by the Gq family of GCPR
Phospholipase Cbeta
Activation of phosphodiesterase results in what effect
Breakdown of cAMP and reduction of downstream results
What is the result of increase in catalytic subunits
Phosphorylation and activation of response elements
What is the result of an increase in phophatase activity
Removal of phosphates and decrease actions of response elements
What is the result of an increase in PLC activity
Increase production of IP3 and DAG from PIP2 leading to more activation
