ICPP 11 - Intracellular Signalling Pathways Flashcards Preview

Introduction to Cell Physiology & Pharmacology > ICPP 11 - Intracellular Signalling Pathways > Flashcards

Flashcards in ICPP 11 - Intracellular Signalling Pathways Deck (14)
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1
Q

Where is 99% of the human bodies 1kg of calcium found?
What is the serum levels of Ca2+ in the body?
How is whole body Ca2+ homeostasis regulated?

A
  • In bone
  • 1.9-2.3mM of which 50% is free Ca2+
  • by intestinal Ca2+ uptake (from diet), Ca2+ reabsorption in kidneys and bone calcium regulation - these are under endocrine control (PTH increases, calcitonin decreases)
2
Q

What kind of processes are (small) changes in IC Ca2+ responsible for?

A

Muscle contraction, neurotransmission, fertilisation, cell death, learning and memory.

3
Q

By what mechanisms are Ca2+ gradients set up and maintained?

A
  • Relative impermeability of PM to Ca2+
  • Pumps and transporters that move Ca2+ out of the cytoplasm
  • Ca2+ buffer proteins.
  • -> PMCA and SERCA move Ca2+ out of the cytoplasm
  • -> NCX moves Ca2+ out of the cell in exchange for Na+
4
Q

Which mechanisms increase IC Ca2+?

A
  • Ca2+ influx via ligand gates ion channels or voltage operated ion channels.
  • Ca2+ movement out of the SER through RyR’s or IP3 receptors (CICR)
5
Q

Describe the signal pathway that occurs when Gs is activated.

A
  • Gs activated, GDP swapped for GTP
  • alpha and beta/gamma subunits dissociate
  • Adenylyl cyclase activated, converts ATP into cAMP
  • cAMP activates PKA which phosphorylates target proteins within cell.
6
Q

Give 3 examples of receptors that are coupled to Gs and their associated ligands.

A

1) B-adrenoreceptors (adrenaline/noradrenaline)
2) D1-dopamine receptors (dopamine)
3) H2-histamine receptors (histamine)

7
Q

Describe the signal pathway that occurs when Gi is activated.

A
  • Gi activated, GDP swapped for GTP
  • Inhibits the activation of adenylyl cyclase
  • Less/no cAMP synthesised
  • Less/no activation of PKA, and therefore intracellular effects lacking.
8
Q

Give 4 examples of receptors coupled to Gi and their associated ligands.

A

1) a2-adrenoreceptors - adrenaline
2) D2-dopamine receptors (dopamine)
3) U-opioid
4) M2/M4 mAChR’s (ACh)

9
Q

Describe the structure of PKA and how cAMP levels regulate its activity.

A
  • Heterotetramer with 2 regulatory subunits attached to 2 catalytic sub-units
  • When cAMP is low, regulatory subunits and catalytic subunits have high affinity for each other, stay bound and inhibit activity of catalytic subunits
  • When cAMP is high, cAMP binds to R sub-units and catalytic subunits dissociate, leading to phosphorylation of target proteins.
10
Q

Describe the signal pathway that occurs when Gq is activated.

A
  • Gq activated, GDP swapped for GTP
  • Activated PLC, causing cleavage of PIP2 into DAG and IP3
  • IP3 acts on IP3 receptors in ER, activating Ca2+ channel and entry of Ca2+ into cytoplasm
  • DAG remains in membrane, binds to PKC which PP’s key substrate proteins
11
Q

Give 3 examples of receptors coupled to Gq and their associated ligands

A

1) a1-adrenoreceptors (adrenaline)
2) M1/M3/M5 mAChR’s (ACh)
3) H1 histamine receptors (histamine)

12
Q

Why is only a few molecules of ligand required to create a massive cellular response in GPCR’s?

A

Due to the large amplification effect that occurs - the step from AC to cAMP is large amplification step, that means we don’t need to waste cellular energy providing large amounts of ligand for receptors.

13
Q

What is the effect of adrenaline binding to B1-adrenoreceptors in the heart on inotropy?

A
  • Activated Gs, increases Ca2+ entry through cascade, increased contractility, and therefore a positive inotropic effect.
14
Q

What is the effect of noradrenaline binding to a1-adrenoreceptors in smooth muscle

A
  • Vasocontriction via the Gq signalling pathway