Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology Midterm (edit) > Lecture 3 Part 2 > Flashcards

Lecture 3 Part 2 Flashcards

1
Q

Gs and other G proteins use a molecular mechanism that involves what?

A

the binding and hydrolysis of GTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what does GDP and GTP stand for?

A

GDP = guanosine diphosphate
GTP = guanosine triphosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

when the GPCR (G protein coupled receptor) is NOT ACTIVATED by a ligand, what is it associated with?

A

guanosine diphophate (GDP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

when the GPCR IS activated by a ligand, what happens?

A

GDP is released and GTP enters the nucleotide binding site of the G protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what happens after the GPCR has been activated by a ligand and GDP has been released and GTP has entered the nucleotide binding site of the G protein?

A

the activated G protein (now bound to GTP) migrates from the receptor and goes to regulate the activity of an EFFECTOR ENZYME or an ION CHANNEL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the potential effectors of an activated G protein (one bound to GTP)

A

-an effector enzyme

-an ion channel (E)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

as mentioned, an activated G protein can regulate the activity of either an effector enzyme or an ion channel (E)

what stops the signal?

A

the hydrolysis of GTP stops the signal and E active –> E

the G protein is now again bound to GDP and couples back with the receptor to await activation

(1 inorganic phosphate is released from GTP-> GDP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

true or false

when the G protein is bound to GDP, it is said to be in an inactive state

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

true or false

once the ligand has activated the G protein to release its GDP and bind to GTP, it doesn’t matter whether or not the receptor ligand is still bound or free

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the rate limiting step in the termination of effector activation in the case of GPCRs?

A

the hydrolysis of GTP to GDP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what determines how long the effect produced by a GPCR will last?

A

the rate limiting step – hydrolysis of GTP to GDP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

true or false

cGMP is not a second messenger

A

false - it is

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

true or false

NE (norepinephrine) works via a G-protein coupled receptor

A

true - it’s a cetecholamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

explain how the rate limiting step for the effect of a G protein is not determined by how long the ligand is bound to the receptor

A

a neurotransmitter like norepinephrine may only encounter its receptor for milliseconds.

but, when the Gs protein coupled to the NE receptor binds GTP and is activated, it may remain active for TENS OF SECONDS – enormously amplifying the original signal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

which 3 subfamilies of G proteins are most important and usual for drugs?

A

Gs
Gi
Gq

Gs = G stimulatory
Gi = G inhibitory
Gq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

name the ligands for Gs

A

beta-adrenergic amines
glucagon
histamine
serotonin
other HORMONES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Further classify Gi subfamily

A

Gi1
Gi2
Gi3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

name the ligands for Gi

A

alpha2-adrenergic amines
acetylcholine (muscarinic)
opioids
serotonin
others

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

name the ligands for Gq

A

acetylcholine (muscarinic)
serotonin (5-HT1C)
many others

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

state the effector/signaling path for Gs

A

increased adenylyl cyclase activity
increased cAMP and calcium channel activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

state the effector/signaling path for Gi

A

decreased adenylyl cyclase
decreased cAMP
cardiac K+ channels open, decreases heart rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the ligands for Golf

A

odorants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

state the effector/signaling path for Golf

A

decreased adenylyl cyclase and decreased cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are the ligands for Go

A

neurotransmitters in the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
state the effector/signaling path for Go
not clear
26
State the effector/signaling path of Gq
increased cytoplasmic calcium all 2nd messengers increased DAG IP3 phospholipase c activity
27
what are the ligands for Gt(1-2)
photons rhodopsin - retinal rods color opsonins - cone cells
28
state the effector/signaling path of Gt(1-2)
increased cGMP phosphodiesterase decreased cGMP (phototransduction)
29
some GPCR's are also called ___________. why?
Serpentine receptors bc the receptor polypeptide chain resembles a snake
30
true or false "serpentine" receptors are GPCR's
true
31
serpentine receptors are GPCR's and are often called....
7 transmembrane spanning receptors
32
explain the structure of serpentine receptors
extracellular amino terminus (N) NH2 intracellular carboxy terminus (C) COOH spans the membrane 7 times consists of extracellular and intracellular loops
33
true or false all GPCR's are serpentine receptors
false - only some
34
in serpentine receptors, is the amino group extracellular or intracellular?
extracellular carboxy group (COOH) is intracellular
35
name 2 potential ligands for serpentine receptors. where does the ligand bind?
catecholamines and acetylcholine binds within the pocket formed by the 7 transmembrane regions
36
after the ligand binds within the pocket of the serpentine receptor, what happens?
there is a conformational change in the receptor. this is sensed by the loops within the cytoplasm and the G protein gets activated (GDP becomes GTP) and dissociates from the receptor GTP gets hydrolyzed back to GDP and the G protein-GDP complex is INACTIVE and couples again with the receptor
37
in serpentine GPCR, what may be associated with diminished interaction between the receptor and G protein?
the cytoplasmic tail of the GPCR contains SERINE and THREONINE residues. these serine and threonine residues can be phosphorylated and this phosphorylation may be associated with diminished interaction between receptor and G protein
38
_________ responses to drugs and hormonal agonists often DESENSITIZE with time
receptor-mediated responses
39
true or false desensitization is usually irreversible
false - usually reversible
40
define desensitization
occurs when even though the receptors are saturated with agonist, the response gradually decreases
41
true or false many kinds of receptors undergo desensitization
true
42
true or false although many kinds of receptors undergo desensitization, the mechanism is not clear in most cases
TRUE - like the nicotinic acetylcholine receptor the beta-adrenoceptor desensitization mechanism, however, has been worked out in some detail
43
explain the mechanism of beta-adrenoceptor desensitization
when the ligand binds, Gs-GTP and bARK (b-adrenergic receptor kinase) is activated. bARK PHOSPHORYLATES the cytoplasmic tail on the serine and threonine residues. this increases the affinity of b-arrestin to bind b-arrestin (protein) then binds to the cytoplasmic tail. this results in a diminished ability for the receptor to interact with the G protein. THUS, THE RESPONSE TO THE AGONIST IS REDUCED
44
In the desensitization mechanism of the b-adrenoceptor, what happens when the agonist is removed?
-phosphatases cleave the phosphates from the cytoplasmic tail (originally placed there by bARK) -bARK activity is decreased (stops phosphorylating the tail of the receptor) -receptor has now "reset" itself and is now ready to fully respond to the agonist
45
in the desensitization mechanism for b-adrenoceptor, why is it that even though the ligand (agonist) is bound, the response will be decreased
the G protein-GDP can't be activated because it can't bind to the 3rd intracellular loop of the receptor -- it is occupied by b-arrestin
46
true or false once the ligand dissociates from the receptor, bARK is inactivated
true
47
when agonist is NOT bound to the receptor, explain what is happening to the beta-adrenoceptor
the inorganic phophates are released, beta-arrestin dissociates from the cytoplasmic tail, and the G protein-GDP complex can now couple with the receptor the receptor has now "reset" itself and is ready again to fully respond to the agonist
48
name 3 well established second messengers
cAMP Ca2+ cGMP
49
what does cAMP stand for
cyclic adenosine monophosphate
50
true or false cAMP is a second messenger
true
51
when and where is cAMP released?
released in the cytoplasm due to hormone binding
52
explain the function of 2nd messengers
they can activate many cell activities leading to a large scale, coordinated response.
53
2nd messenger mechanism - cAMP
-agonist binds -this activates Gs and Adenylyl Cyclase. ATP converted to cAMP by Adenylyl cyclase. cAMP converted to AMP by PDEs (phosphodiesterases) cAMP kinase: consists of catalytic region and regulatory region. cAMP binds to the regulatory sites and the catalytic regions are released. catalytic regions + ATP will phosphorylate the substrate leadinf to a CELLULAR RESPONSE: -enzyme activation -protein synthesis -muscle relaxation -nerve stimulation -hormone secretion
54
what is the function of AC in the mechanism of second messengers
AC = adenylyl cyclase converts ATP to cAMP
55
what does cAMP get converted to and by what
cAMP is converted to AMP by PDEs (phosphodiesterases)
56
explain the structure and role of cAMP kinase
consists of 2 regulatory regions and 2 catalytic regions. cAMP binds to the regulatory sites which releases the catalytic regions. these catalytic regions + ATP phosphorylate the substrate to produce a cellular response
57
explain the cellular response produced by cAMP
-enzyme activation -protein synthesis -muscle relaxation -nerve stimulation -hormone secretion
58
true or false cAMP causes muscle stimulation
false - muscle relaxation
59
true or false cAMP causes nerve stimulation
true
60
true or false cAMP causes enzyme activation
true
61
true or false cAMP causes protein degradation
false - protein synthesis
62
true or false cAMP causes hormone secretion
true
63
what is the mechanism of viagra
phosphodiesterase inhibitor. this will prevent the conversion of cAMP to AMP this will increase cAMP causing an increase in downstream signaling and vasodilation (muscle relaxation)
64
in the mechanism of cAMP, what happens when the agonist dissociates?
the intracellular actions of cAMP are terminated by 3 mechanisms: -GTP hydrolyzed back to GDP -the activation of cAMP kinase is inhibited. the Tetramer is re-established -the phosphorylated substrate (generated by cAMP kinase) is dephosphorylated (BY PHOSPHATASES), causing a DIMINISHED CELLULAR RESPONSE
65
What is the effect of caffeine on cAMP levels?
caffeine acts as a competitive inhibitor of phosphodiesterases, thus INCREASING CAMP LEVELS
66
Besides caffeine, what drugs increase cAMP levels?
theophylline (bronchodilator used for asthma treatment) methylxanthine drugs
67
what substances are COMPETITIVE INHIBITORS of PDEs? (phosphodiesterases)
caffeine and theophylline methylxanthine drugs are non competitive inhibitors of phosphodiesterases
68
true or false caffeine, theophylline, and methylxanthine drugs all increase intracellular cAMP levels
true
69
name 5 effects of methylxanthine drugs
- increased CNS activity (increased alertness, deferral of fatigue) -increase in inotropic effect of the heart (increase force) -increased gastric acid secretion and increased enzymes (in GI) - decreased Na reabsorption and increased glomerular filtration (thus they are weak diuretics!) -increased bronchodilation (used for asthma treatment!)
70
true or false methylxanthines decrease heart contraction
false - increase
71
true or false methylxanthines increase gastric secretion and enzymes in the GI tract
true
72
true or false methylxanthines decrease sodium reabsorption
true also increase glomerular filtration -- weak diuretics
73
what effect do methylxanthines have on the CNS?
increased CNS activity leading to increased alertness and deferral of fatigue
74
what is(are) the second messenger(s) involved in Gq coupled receptors
calcium and phosphoinositides
75
name 4 receptors that are Gq coupled
acetylcholine (muscarinic) alpha1-adrenergic platelet activating factor serotonin (5-HT1C and 5-HT2)
76
When a ligand is bound to Gq, what 2nd messenger is likely involved?
calcium
77
explain the mechanism of calcium as a second messenger
agonist binds, Gq protein is stimulated and binds GTP. PLC activates PIP2 which activates DAG and IP3. IP3 releases CALCIUM. this calcium binds and activates CALMODULIN. calmodulin (with bound calcium) then stimulates signaling through calcium/calmodulin dependent protein kinases to PHOSPHORYLATE THE SUBSTRATE AND PRODUCE A CELLULAR RESPONSE meanwhile, while IP3 released calcium, DAG remains in the membrane where it binds and activates PKC (protein kinase C) which phosphorylates certain substrates to produce a cellular response -- INCREASED GLAND SECRETION, CELL GROWTH AND DIFFERENTIATION, AND INCREASED METABOLISM
78
how does PKC become active and what happens when it is activated
DAG binds and activates PKC. PKC can then phosphorylate certain substrates to produce a cellular response
79
what cellular responses occur when PKC phosphorylates its substrates
increase gland secretion increased cell growth and differentiation increased metabolism
80
what does cGMP stand for
cyclic guanosine-3',5'-monophosphate
81
explain where cGMP plays a role as a second messenger
only in a few cell types like intenstinal mucosa and vascular smooth muscle
82
explain whne cGMP-based signal transduction is initiated. in which cells does this occur?
in intestinal mucosa and vascular smooth muscle when: -ligand binds to the extracellular domain of the receptor -ligand binding stimulates intracellular guanylyl cyclase activity -cGMP activates cGMP-dependent protein kinases
83
what is cGMP produced from and how?
GTP becomes cGMP through guanylyl cyclase guanylyl cyclase activity is stimulated when the ligand binds to the extracellular domain of the receptor
84
what does cGMP do
it activates cGMP dependent protein kinases these activated kinases then phosphorylate the substrate
85
increased cGMP causes....
relaxation of vascular smooth muscle
86
HOW does cGMP cause the relaxation of vascular smooth muscle?
by a kinase-mediated mechanism that results in the DEPHOSPHORYLATION of myosin light chains
87
name 2 specific things that will result in increased cGMP accumulation
-ANP binds to its receptor which increases guanylyl cyclase activity. guanylyl cyclase converts GTP to cGMP -lipid souble gas NO (nitric oxide) is released by nearby vascular endothelial cells which DIRECTLY ACTIVATES guanylyl cyclase (binds to it and activates)
88
several _____ drugs mimic NO (nitric oxide)
vasodilator
89

Pharmacology Midterm (edit) (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions