G protein Coupled Receptors

Question 1

Sturcture of the GPCR

Answer 1

Seven emembrane spanning receptors

Question 2

Drugs targeting at GPCR: cetirzine

Answer 2

allergy at H1 antagonist

Question 3

Drugs targeting at GPCR: atropine

Answer 3

gastrointestinal, muscarninc antagonist

Question 4

Drugs targeting at GPCR: Fingolimod

Answer 4

multiple sclerosis at sphingosine 1-PO4 agonist

Question 5

Drugs targeting at GPCR: Phenylephrine

Answer 5

nasal congestion,
a1 agonist

Question 6

Drugs targeting at GPCR: Formoterol

Answer 6

asthma, B2 agonist

Question 7

Drugs targeting at GPCR: Montelukast

Answer 7

Asthma at LTD4 antagonist

Question 8

Drugs targeting at GPCR: Losartan

Answer 8

Hypertension at AT1 antagonist

Question 9

Drugs targeting at GPCR: Propranolol

Answer 9

hypertension at B antagonist

Question 10

three components of the GPCR signaling

Answer 10

when the signal reaches the receptor, the receptor casues the Gprotein GDP to become GTP, and the GTP binds to the effector and the effector is activated adn the signal is trasnduced

Question 11

where do formoteroal bind ad what happens after that

Answer 11

binds to the b2 receptor adn result in the “a simulation” resulting in ATP to become CAMP adn the cyclinc AMP dependent protein kinase which will bind to the enzyems and ion channels

• CAMP will be convered to amp by the phsophodiesterase

and PKA becomes CREB

Question 12

where does clonidine binds and what happens

Answer 12

binds to the a2 receptor and result in the “a inhibitor” resulting in decresaed conversion of ATP into CAMP

Question 13

what happens when phenlephrine binds and to what does it bind

Answer 13

binds ot the a1 receptor adn result in the “a EFFECTOR” to bind ot the phospholipase Cb
PLCB result in the PIP2 to become IP3 and DAG
IP3 result in the ER to release the Ca2+ which bidns to ca calmodulin and this result in the signlaing

DAG result in the Protein kinase C
PKC result int PLA2 to convert phospoholipids to become arachidonic acid
PKA result in c fos and c junciton asd well

Question 14

what happens to Rhodopsin when it binds to the receptor

Answer 14

when it binds to the receeptor, it resule in the g protein trasnducin to release, the tranducin will actiivate cGMP specific PDE and thie decreases cgmp levels, and when it drops, Na and Ca channel closes, in a process called hyperpolarisation,

when the brain recieve the signal, the drop in ca activates cytosolic guanylyl cyclase , increase in cgpm reopens na and ca channel
the cycel of photoreceptr signalling starts again

Question 15

how is g protein recycled

Answer 15

it has GTPase that result in the reproduction of the GDP in state 1

Question 16

how is signal amplified

Answer 16

receptor activate alot fo GTP, alot of GTP activate more Effectors, and more second messangers

Question 17

how are the receptors reglated for the GPCR

Answer 17

1. ligand removal
2. desensitization
   - uncoupling of the receptor, gprotein, effector
   - internilisaiton and relocation and compartmentalization
   -down regulation by reduced synthesis and proteolytic degradation

Question 18

drugs that result in the receptor regualation and where they act

Answer 18

formoterol -b2 adrenergic receptor agonist - anti asthma drug - anti asthma drug
phenylphrine-a1 adrenergic receptor agonist-nasal desongestant
morphine- opioid receptor agonist-analgesic

Question 19

what are the actions when the receptor is being regulated

Answer 19

phospohrylated by the b arrestin and then the clathrin coacted pit would be moved inside and the recept would be internalsied. Lysosme can bind to it and resultin the down regulation if there are alot of receptors ?

Question 20

GRK s and arrestin

Answer 20

GRK1: rhodopsin kinase
GRK2: B adrenegric receptor kinase 1
GKR3: B adrenegric receptor kinase 2
GRK4, 5, 6, 7,

ARRESTIN
cone
rod
B arrestin 1
b arrestin 2

Question 21

types of receptor desensitiaation

Answer 21

homologous: the effect only affects the specific receptor

heterologous: affects related receptors as well