Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Patho 2023 > Watts Set 3 > Flashcards

Watts Set 3 Flashcards

1
Q

what are the 5 classes of receptors

A

intracellular receptors
cytokine receptors
protein kinase receptors
ion channels
GPCRs

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

what are intracellular receptors

A
  • Intracellular receptors (regulate gene expression) (steroids)
    — Stimulate the transcription of genes
    – Additional non receptor receptors
    ——– Effector enzymes that regulate cellular function include membrane potential, protein phosphorylation, translation, transcription, etc.
    ———–> Kinase, cyclase, phosphatases, ubquitinases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are cytokine receptors

A

simplest
- JAK-STAT pathway
- mechanism: binds, activation leads to JAK, phosphorylation to STAT, dimerizes and travels to regulate transcription
–> Examples: GHs, erythropoietin, interferons

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

what are protein tyrosine kinase receptors

A
  • Mechanism: ligands dimerize,conformational change, phosphorylation happens and recruits GRAB, leads to activation of RAS, RAS leads to transcription
    —> Examples, EGF, PDGF, insulin
  • This pathway can be turned off by blocking
  • Receptor tyrosine kinases as drug targets
    —> Lots of ways to target an receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the two types of ion channels

A

voltage gated and ligand gated

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

what do voltage gated ion channels do

A
  • No ligand just membrane potential
  • Bind at allosteric sites
  • In order to block we have to activate
    –> Ex: na, ca,k
  • Involved in pain, epilepsy, arrhythmias, vascular tone, neurotransmitter release
  • Channels can be regulated by phosphorylation and G proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what do ligand gated ion channels do

A
  • Many drugs act by mimicking or blocking endogenous ligands that regulate flow of ions through channels
    –> Ex: acetylcholine, gamma-aminobutyric acid, glutamate, etc.
  • When bind the signal is transmitted across membrane and alters electrical potential
  • Very fast (milliseconds)
    –> Important in rapid transfer of signals across synapses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are g couples protein receptors

A
  • Very popular in human genome and largest family
  • 40% of drugs target GPCRs
  • 3 classes (A,B,C)
  • Ligands act by modulating effectors and concentrations of second messengers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

who invented cyclic AMP in 1971

A

earl sutherland

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

what are the features of G protein activation

A
  • effectors: channels, enzymes, regulatory proteins
  • second messengers: cAMP, CA2+, phosphoinositides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the components of the signaling process for gpcrs

A

R
- extracellular ligand is detected by cell surface receptor
G
- this receptor in turn trigger activation of G protein located on cytoplasmic face of the plasma membrane
E
- activation of Galpha and Gamma/beta then changes the activity of the effector
– enzyme or ion channel
- this effector often changes the concentration of the intracellular second messengers which produce an effect
– greatly amplified response

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

what are the subtypes of G proteins

A

Gas, Gai, Gaq/11, Ga12/13, Gby

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

what is Gas effector

A

inc. adenylyl cyclase

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

what is Gas isoforms

A

gas, golf

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

what is Gai effectors

A

dec. adenylyl cyclase

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

what is Gai isoforms

A

Gai1, Gai2, Gai3

17
Q

what is Gaq/11 effectors

A

inc. phospholipase C

18
Q

what is Gaq/11 isoforms

A

Gaq

19
Q

what is Ga12/13 effectors

A

recruit Rho guanine exchange factors

20
Q

what is Ga12/13 isoforms

A

Ga12, Ga13

21
Q

what is Gby effectors

A

dec. adenylyl cyclase
inc. ion channels (Ca and K)

22
Q

what is Gby isoforms

A

B (1-5)
y (1-13)

23
Q

what are the second messengers

A

cAMP
cGMP
calcium and phosphoinositides

24
Q

what does the second messenger cAMP do

A
  • Effector enzyme is adenylyl cyclase and enzyme that converts ATP to cAMP
  • cAMP stimulates PKA
  • Specificity of cMAP is defined by compartmentalization of signaling complexes
    — Ex: B1 adrenergic receptors for asthma
25
Q

what does the second messenger cGMP do

A
  • Effector enzyme is guanylyl cyclase
  • cGMP activates PKG
  • Regulated by nitric oxide
  • Much more specific than other messenger systems
26
Q

what do the second messengers calcium and phosphoinositides do

A
  • PLC results in release of phosphoinositides and diacylglycerol
  • Phosphoinositides result in release of calcium
  • Diacylglycerol active protein kinase C
    –> Ex: muscarinic receptors in alzheimers
27
Q

what are kinases

A

phosphorylation
- 800 genes in genome
- unique specificity
- inhibitors as drugs:
–> imantinib, trastuzumab

28
Q

what are phosphatases

A

dephosphorylation
- 250 genes in genome
- very few drugs targets
—> ex: diabetes, PD, AD, allergy and asthma

29
Q

what is the mechanism and consequence for homologous desensitization

A
  • Does it to itself
  • Rapid desensitization
    – GRKs aka B-ARK
    – Less responsive
  • Receptor uncoupling-arrestin binding
  • Sequestration and fate (arrestin involvement)
    — Recycling (dephosphorylation)
    — Degradation (lysosomal degradation)
30
Q

what’s the mechanism and consequence for heterologous desensitization

A
  • Can do this to another receptor with kinases
  • non-agonist/receptor-specific
  • Involve signaling cascades from other receptors
    — PKA or PKC phosphorylate receptor of interest
  • Blunt receptor response or alter G protein coupling
31
Q

how can we use functional selectivity to design better drugs

A

we can use them to enhance therapeutic pathway
- TRV027-AT1 biased agonist that promotes B arrestin
– Blocks vasoconstriction in HF
– Beneficial in COVID
- Opioid therapy for analgesia
– B arrestin linked to tolerance and maybe respiratory depression
– Avoid this pathway
– we want the G protein pathway here

32
Q

what is functional selectivity and its purpose in concentration response curves

A
  • AKA agonist trafficking, biased agonism, ligand bias, differential engagement, and protein agonism
  • Requires the receptor couple to multiple signal transduction pathways
    – G protein and B arrestin
  • Display selectivity for one or more pathways when compared to another pathway
  • Receptor binding to other pathways
33
Q

tell me about the Diversity of Gs-AC-cAMP system for cAMP

A

many different pathways and combinations; very diverse

34
Q

tell me about the Diversity of Gq-PLCAC-IP3/DAG system for calcium and phosphoinostides

A

Gq-linked receptors
- Multiple types
- Cleaves PIP2 to produce DAG that leads to protein kinase C, IP3 that leads to production of calcium

35
Q

what are the significances of intracellular receptors

A

— Significances:
———– Has lag period and slow
———– Cannot be altered in minutes, takes hours
———– Effects can persist after conc. Is reduced to zero
———– Slow turnover
—————-> May be due to high affinity

36
Q

what is the mechanism for intracellular receptors

A

— Mechanism: steroid, ligand binding domain, dna binding domain, altered transcription of gene

37
Q

how can we measure the second messenger cAMP

A

Measure by:
- many ways
- Radioactive assays are not popular anymore

Patho 2023 (37 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions