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pharmacology > Principle of cellular physiology 3 > Flashcards

Principle of cellular physiology 3 Flashcards

1
Q

What does the first G protein discovered contain and what does is activate?

A
  • Contained an alpha subunit
  • Could activate adenyl cyclase (AC)
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2
Q

What are the different subunits of this G protein?

A
  • Alpha s which stimulates AC
  • Alpha i which inhibits AC
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3
Q

What do beta-adrenoreceptors couple to?

A

Gs

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4
Q

What do alpha 2 adrenoreceptors couple to?

A

Gi

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5
Q

G alpha q proteins allow hormones/neurotransmitters to activate which enzyme?

A

The amplifier enzyme phospholipase C (PLC)

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6
Q

Describe the stages leading to muscle contraction involving Gq proteins.

A
  • Gq proteins stimulate PLC
  • PLC splits PIP2 into IP3 and DAG
  • IP3 is water soluble so travels through the cytosol and stimulates calcium release from ER
  • DAG remains in the membrane where it recruits protein kinase c (PKC)
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7
Q

Describe the stages of calcium mediated intracellular responses.

A
  • Each Calmodullin (CaM) binds to 4 Ca2+ ions
  • Ca2+-CaM complex activates CaM kinases (CaMKs)
  • CaMKs phosphorylates Serine and Threonine residues on substrate proteins
  • alpha 1 adrenal-receptor mediates vascular smooth muscle contraction by increasing intracellular free Ca2+ activating CAMKs (vasoconstriction)
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8
Q

What are CaMKs involved in?

A

Smooth muscle contraction

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9
Q

What are the effects of DAG?

A
  • DAG is hydrophobic and so remains in the plasma
    membrane where it can increase the activity of Ca2+ dependent kinases
  • Evokes cellular responses by phosphorylating other
    proteins. The most important one is proteins kinase C
    (PKC)
  • PKCs can potentiate the effects of IP3
  • Regulates cell shape, cell proliferation and
    transcription factor activity
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10
Q

Describe the role of alpha 1 adrenoreceptors in blood pressure control.

A
  • Causes vascular smooth muscle tone contraction
  • Via Gq-PLC-IP3
  • leads to increased blood pressure
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11
Q

Describe the role of beta 2 adrenoreceptors in blood pressure control.

A
  • Causes relaxation of vascular smooth muscle
  • Via Gs-cAMP-PKA
  • leads to decreased blood pressure
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12
Q

What are muscarinic receptors?

A

Gq/Gi coupled receptors

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13
Q

What activates muscarinic receptors?

A

ACh

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14
Q

How many subtypes are there of muscarinic receptors?

A
  • 5
  • 1-3-5 Gq coupled stimulatory
  • 2-4 Gi coupled inhibitory
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15
Q

What are the 4 enzyme linked receptors?

A
  1. Receptor guanylyl cyclases
  2. Receptor serine/threonine kinase
  3. Receptor tyrosine-kinase
  4. Receptor tyrosine phosphatase
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16
Q

Describe the structure of guanylyl cyclase.

A
  • Contains 2 transmembrane domains which convert GTP to cGMP
  • cGMP activates downstream kinases
16
Q

What is the mechanism of signalling of guanylyl cyclase?

A
  1. Binding of ligand induces a conformational change in the receptor - causes receptor dimerisation and activation
  2. The Guanylyl cyclase activity of the receptor generates cGMP
  3. Increased concentrations of cGMP activates other signalling molecules determining the response
  4. Example of responses: relax vascular smooth muscle and dilate blood vessels vasodilation
17
Q

Describe receptor serine/threonine kinases.

A

Contain serine-threonine kinase domains which phosphorylate target proteins.

18
Q

Describe the mechanism of signalling for receptor serine serine/threonine kinases

A
  1. First messenger binds to receptor Type 2
  2. Receptor Type 1 then binds forming ternary complex with Type 2 and first messenger
  3. Type 2 receptor phosphorylates Type 1, activating the Ser-Thr kinase activity of Type 1
  4. Type 1 then phosphorylate target proteins
  5. Example of responses: cell proliferation
19
Q

Describe receptor tyrosine kinases.

A

obtain tyrosine kinase domains which phosphorylate tyrosine residues on many RTKs

20
Q

Describe the mechanism of signalling for receptor RKTs

A
  1. Binding of insulin causes the receptor to dimerise
  2. Then uses their cytoplasmic try kinase activity to phosphorylate each other - each RTK in the dimer phosphorylates multiple tyrosines on other RTK
  3. Then they recruit intracellular signalling molecules leading to the response
  4. Example of response: insulin mediated glucose uptake and storage in liver and muscles
21
Q

Describe receptor tyrosine phosphatase

A

Contain tyrosine phosphatase domains and deposphorylate target proteins

22
Q

Describe the mechanism of signalling for receptor tyrosine phosphatase.

A
  1. Ligand binding to the receptor inducing a conformational change that activates the Tyr phosphate activity of the receptor
  2. Target proteins are dephosphorylated by Tyr phosphatase activity
  3. This cause the regulation of downstream cell-signalling events
  4. Response examples: maturation of lymphocytes

pharmacology (40 decks)

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