Pathophysiology and Drug Action Exam 2 (Set 3)

Question 1

Identify and differentiate between the five classes of receptors

Answer 1

Intracellular receptor, receptor that converts substrate into a product, receptor that leads to phosphorylation on a tyrosine residue, ion channel, G protein coupled receptor

Question 2

Describe the effects of allosteric modulators on Ion channels and GCPRs

Answer 2

-bind to areas other than the orthosteric binding site
-more favorable than channel blockers because they can target channels more specifically and regulate their activities more precisely

Question 3

Describe the features of G protein activation

Answer 3

signaling system has three components (R-G-E)
Starts will cell-surface receptor(R)-triggers activation of (G) protein-activated Ga or Gby protein changes activity of an effector(E) element usually an enzyme or ion channel

Question 4

What is the G protein cycle?

Answer 4

Ga-GDP=inactive
Ga-GTP or GBy=active
enzyme or channel activated results in release of second messengers

Question 5

name the effectors of subtypes of G proteins

Answer 5

G Protein | effectors
Ga(s)-upregulates Adenyl Cyclase, Src family tyrosine kinases
Ga(i)- downregulates adenyl cyclases, upregulates Phosphodiesterases
Ga(q/11)- Upregulates Phospholipase C 1B
Ga(12/13)- recruites Rho guanine exchange factors
Gby-downregulates adenyl cyclases, recruits GRK2/3, upregulates PI3Ky, Ion channels (Ca2+ and K+)
5 B subunits; 12 Y subunits

Question 6

What is signaling of second messengers like?

Answer 6

signaling for second messengers-
cAMP effector enzyme: adenylyl cyclase; coverts ATP to cAMP
Gs-AC-cAMP system is very diverse and complex
Calcium and phosphoinosotides
effector enzyme: phospholipase C (PLC); releases phosphinositides and diacylglycerol
Gq-PLCAC-IP3/DAG very diverse and complex
cGMP
effector enzyme: guanyl cyclase
activates PKG (cGMP-dependent protein kinase)
regulated by nitric oxide

Question 7

What is signaling of arrestin like?

Answer 7

desensitization (G protein uncoupling; 2nd messenger degradation)
endocytosis (recycling/lysosomal degradation)
signaling (chemotaxis, apoptosis, metastasis, protein transportation)

Question 8

describe the mechanism and consequence of receptor desensitization

Answer 8

Homologous desensitization- a receptor decreases its response to an agonist at high concentration; after prolonged agonist exposure, the receptor is uncoupled from its signaling cascade and receptor activation is halted
1. rapid desensitization (GRKs)
2. receptor uncoupling-arrestin binding
3. sequestration and fate of the receptor…
recycling or lysosomal degradation

Question 9

What is heterologous sensitization?

Answer 9

-inhibitory receptors (Gi-linked)
-enhance receptor response or alters G protein coupling to stimulate AC-cAMP

Question 10

What is heterologous desensitization?

Answer 10

one receptor desensitizing another

Question 11

What is functional selectivity?

Answer 11

-a ligand will display selectivity for one or more pathways when compared to another pathway
-most extensively characterized at G protein coupled receptors
-biased signaling

Question 12

Which of the following is NOT true regarding spare receptors?
A. It is system/tissue dependent
B. Allow a noncompetitive irreversible antagonist to look like a competitive antagonist
C. Spare receptors reveal functional receptor response at low receptor occupancy
D. Show the same response for all signaling pathways with the same receptor

Answer 12

D. Show the same response for all signaling pathways with the same receptor

Question 13

Which of the following is NOT true regarding antagonists?
A. Irreversible and allosteric antagonists have similar effects on the dose response curves of agonists
B. In the absence of spare receptors, a noncompetitive antagonist decreases the Emax
C. Irreversible antagonists typically bind the allosteric site
D. Angtagonist KD values can be estimated using a Schild plot

Answer 13

C. Irreversible antagonists typically bind the allosteric site

Question 14

Which receptor subtype is most likely to be involved with an extremely fast drug response?

Answer 14

Ligand-gated channel

Question 15

Which receptor subtype os most likely to be involved with an extremely slow drug response?

Answer 15

steroid hormone receptor

Question 16

Which receptor subtype is capable of modulating gene expression?

Answer 16

-G-protein coupled receptor
-Steroid hormone receptor
-Ligand-gated channel
-Tyrosine kinase and cytokine receptor

Question 17

Which of the following G proteins is not matched with its primary effector?
a) Gq-activates phospholipase C
b) Golf- activates guanyl cyclase
c) Gs- stimulates adenylyl cyclase
d) Gi-inhibits adenylyl cyclase

Answer 17

Golf- activates guanylyl cyclase
(activates adenyl cyclase)

Question 18

Which of the following are NOT involved in the mechanism of cellular/pharmacological tolerance of GPCRs:
a) Activation of the receptor by agonist
b) B arrestin-mediated sequestration of the G protein subunit
c) trafficking of the receptor to lysosomes for degradation
d) Phosphorylation of the receptor by G protein-coupled receptor kinases (GRKs)

Answer 18

b) B arrestin-mediated sequestration of the G protein subunit