neuropharmacology: GPCRs

Question 1

how many transmembrane proteins are there in GPCRs?

Answer 1

7 transmembrane proteins in GPCRs; a heptahelical receptor

Question 2

what do g proteins consist of?

Answer 2

g protein consistsof alpah beta and gamma subunit

GDP is bound to alpha subunit
beta and gamma subunits form a dimer

Question 3

what happens when agonist binds to G protein

Answer 3

agonist binding promotes exchange of bound gdp to alpha subunit for gtp
alpha subunit and beta gamma dimer dissociate.
both alpha and bg dimer can associate with or activate or inhibit effectors

Question 4

what are the primary effectors of the beta gamma dimer?

Answer 4

ion channels such as GIRKs, ( g protein regulated inwardly rectifying k+ channels)

Question 5

what are the 4 classes of G proteins

Answer 5

Gs: activates adenylate cyclase, activates cAMP signalling

Gi/o: Gi: inhibits adenylate cyclase
Go: regulates potassium and calcium ion channels

Gq: stimulates phospholipase C, acitvates IP3 and DAG signalling

G12/13: activates Rho to regulate actin cytoskeleton

Question 6

what activates/ inactivates G proteins

Answer 6

activates: alpha subunit switching bound GDP for GTP
inactivates: hydrolysis of alpha subunit bound GTP to GDP

Question 7

what are GEFs?

Answer 7

guanine exchange factors
GPCRs act as GEFs
GEFs are proteins involved in activation of GTPases

Question 8

where does the alpha 12/13 subunit bind to?

Answer 8

RGS domain of Rho proteins

Question 9

what do small GTPases act as?

Answer 9

molecular switches in signalling

Question 10

how much the membrane need to be depolarised to cause AP?

Answer 10

15mV of depolarisation at axon hillock

Question 11

where are GPCRs found

Answer 11

typically they are extra synaptic

Question 12

what is difference between ion channels and GPRCs in terms of once agonist has bound

Answer 12

GPRCs are slow to stop, requires removal of NT and of secondary messenger

Question 13

how do ligand gated ion channels and GPRCs vary in post synaptic potential produced

Answer 13

ligand gated ion channels produce fast ESPS with higher amplitude which does not last as long since when it is activated ions are allowed straight in

GPRCs are slower because 2nd messenger are arriving at ion channels at different times so there is a longer but lower amplitude of influx of ions

Question 14

what effects can second messenger have

Answer 14

affect ion channels, metabolites in cytoplasm, effect gene expression, different GPCRs can exert different effects on same enzyme

Question 15

what kind of GPCRs are D1 and D2 receptors

Answer 15

dopamine receptors:

D1 are Gs and D2 are Gi

Question 16

how may GPCR be drug targets in schizophrenia?

Answer 16

Schizophrenia thought to be caused be excessive dopamine transmission. especially D2 receptors

blocking D2 receptors in basal ganglia and cerebellum cause undesirable side effects, motor dysfunction, akinesia, spasticity and tremors