LEC 2

Question 1

INTRACELLULAR RECEPTORS what are characteristics of drugs that bind to intracellular receptors (2)

Answer 1

1. hydrophobic

2. lipid soluble

Question 2

INTRACELLULAR RECEPTORS what is mech of action

Answer 2

1. drug crosses PM
2. drug binds intracellular receptor
3. receptor displaces HSP to expose DNA binding site
4. receptor translocates to nucleus
5. receptor binds to DNA
6. receptor activates transcription of target gene

Question 3

INTRACELLULAR RECEPTORS what are characteristic effects of drug binding to intracellular receptor

Answer 3

1. slow onset

2. long lasting

Question 4

G PROTEIN (TRANS MEM) what are G protein subunits

Answer 4

1. alpha
2. beta
3. gamma

Question 5

G PROTEIN (TRANS MEM) what happens at rest

Answer 5

1. GDP bound to G alpha

2. G alpha bound to recepotr

Question 6

G PROTEIN (TRANS MEM) what happens when ligand binds to recepotr

Answer 6

GDP GTP excahnge

Question 7

G PROTEIN (TRANS MEM) what does GTP GDP exchange result in

Answer 7

• G alpha unbinds from receptor + acts as effector

- G beta gamma unbinds from receptor + acts as effector

Question 8

G PROTEIN (TRANS MEM) what is molecular timer mech referring to

Answer 8

G alpha hydrolyzes GTP to return sys to rest

Question 9

G PROTEIN (TRANS MEM) what happens to G beta gamma after unbinding from receptor

Answer 9

remains associated w PM

Question 10

G PROTEIN (TRANS MEM) what are 3 G alpha subtypes

Answer 10

1. G s
2. G i
3. G q

Question 11

G PROTEIN (TRANS MEM) what does Gs target

Answer 11

adenylyl cyclase to activate

Question 12

G PROTEIN (TRANS MEM) what does Gi target

Answer 12

adenylyl cyclase to inactivate

Question 13

G PROTEIN (TRANS MEM) what does Gq target

Answer 13

phospholipase C to activate

Question 14

G PROTEIN (TRANS MEM) what does G alpha have indirect effect on

Answer 14

first components of signalling cascade

Question 15

G PROTEIN (TRANS MEM) what is Gs mech (7)

Answer 15

1. agonist binds to receptor
2. receptor changes conformation
3. GTP bound Gs activates AC
4. AC converts ATP to cAMP
   5 cAMP activates protein kinase A
5. protein kinase A phosphorylates substrate
6. phosphorylates substrate generates biological response

Question 16

G PROTEIN (TRANS MEM) what is Gi mech (7)

Answer 16

1. agonist binds to receptor
2. receptor changes conformation
3. GTP bound Gi inhibits AC
4. suppress cAMP
5. suppress protein kinase A
6. suppress phosphorylated substrate
7. suppress biological response

Question 17

G PROTEIN (TRANS MEM) what is Gq mech

Answer 17

1. agonist binds receptor
2. receptor undergoes conformational change
3. GTP bound Gq activates PLC
4. PLC hydrolyzes PIP2 ==> PIP3 and DAG

PIP 3

a. IP3 binds to ER
b. ER releases Ca
c. Ca binds to calmodulin
d. Ca-calmodulin complex binds to effector protein
e. effector protein generates biological response

DAG

a. DAG activates protein kinase C
b. protein kinase C phosphorylates substrate
c. phosphorylated substrate generates biological response

Question 18

TKR (TRANS MEM) what happens when ligand binds to TKR

Answer 18

1. dimerization
2. phosphorylation ==> each other
3. phosphorylation ==> substrate

Question 19

TKR (TRANS MEM) what makes TKR diff from G protein

Answer 19

TKR acts as kinases

Question 20

INTRACELLULAR VS MEM BOUND what is circulating form of drug

Answer 20

1. intracellular ==> bound

2. mem bound ==> variable

Question 21

INTRACELLULAR VS MEM BOUND what is speed of response

Answer 21

1. intracellular ==> slow

2. mem bound ==> fast

Question 22

INTRACELLULAR VS MEM BOUND why is speed of response slow for intracellular (2)

Answer 22

1. requires DNA binding

2. requires activating target genes

Question 23

INTRACELLULAR VS MEM BOUND how fast is termination of signal

Answer 23

1. intracellular ==> slow

2. mem bound ==> fast

Question 24

INTRACELLULAR VS MEM BOUND why is termination slow for intracellular(2)

Answer 24

1. large reserve of bounddrug

2. gene expression is slow to reverse

Question 25

ION CHANNEL what is fastest mech for signalling

Answer 25

ion channel

Question 26

ION CHANNEL what happens when ions cross PM

Answer 26

change in mem voltage

Question 27

ION CHANNEL what are 2 types

Answer 27

1. ligand gated ion channel | 2. voltage gated ion channel

Question 28

ION CHANNEL what is ligand gated ion channel

Answer 28

pore in channel opens in response to binding of ligand

Question 29

ION CHANNEL what is voltage gated ion channel

Answer 29

pore in channel opens in response to changing of voltage

Question 30

what is on x axis of conc response curves

Answer 30

conc

Question 31

what is on y axis of conc response curves

Answer 31

effect

Question 32

what relationship exists bw agonist conc and effect

Answer 32

saturating

Question 33

what is E max

Answer 33

max biological effect

Question 34

what is EC50

Answer 34

conc of drug that produces 50% E max

Question 35

what are2 ways of plotting conc

Answer 35

1. linear scale | 2. log

Question 36

what does linear scale result in

Answer 36

saturating response

Question 37

what does log scale result in

Answer 37

sigmoidal response

Question 38

what does efficacy refer to

Answer 38

mag of E max

Question 39

what does large efficacy mean | what does small efficacy mean

Answer 39

- large efficacy ==> high Emax | - small efficacy ==> low Emax

Question 40

what does potency refer to

Answer 40

EC50

Question 41

what does weakly potent mean

Answer 41

high EC50, large concentration of drug required to generate half Emax

Question 42

what does strongly potent mean

Answer 42

low EC50, low concentration of drug required to generate half Emax

Question 43

what is full agonist

Answer 43

binds to receptor to generate E max

Question 44

what is partial agonist

Answer 44

binds to receptor to generate partial E max

Question 45

what is antagonist

Answer 45

binds to receptor to generate no effect (on own)