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Neuropharmacology > Receptors > Flashcards

Receptors Flashcards

1
Q

Briefly describe the discovery of receptors

A
  1. Langley (1905) poured a solution of nicotine on frog’s legs (observed the muscles twitching after only a few milliseconds)
  2. Dale (1914) poured a solution of muscarine on frog’s legs (observed the muscles twitching after a few tens of seconds)
  3. the conclusion was that there must be some excitable structure that responded to ACh (but must have two different types because of the time difference in responses)
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2
Q

What is bioassay?

A

Using living or part of living creature to test experiments

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3
Q

Describe ligand-gated ion channels (i.e. ionotropic receptors)

A

all have 5 subunits (the subunit composition can vary in the proteins that make up the pentomere)
- ligand-gated is the fastest reacting receptor (ms) but is very short lived, because the pore is not open for long

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4
Q

What happens if the ionotropic pore is permeable to positive ions, like Na+ and K+?

A

The reaction will be excitatory

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5
Q

What happens if the ionotropic pore is permeable to negative ions, like Cl-?

A

Reaction will be inhibitory

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6
Q

What happens if the ionotropic pore is permeable to calcium (Ca2+)?

A

The reaction will be modulatory

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7
Q

What is one example of a ligand-gated ion channel?

A

nAChR (the nicotinic acetylcholine receptor)

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8
Q

Why are nuclear/steroid receptors so potent?

A

They can cross the cell membrane easily because they are fat soluble

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9
Q

How long do steroid receptors typically take to have their effect?

A

about 1-2 hours

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10
Q

Why does it take so long for the steroid receptors to have an effect?

A

Because it is a gene transcriptor

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11
Q

What is a transcriptor?

A

Anything that decides how a gene is expressed

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12
Q

What is the cascade when a ligand binds to a steroid receptor?

A

receptor dimerizes (pairs up) > the pair moves to the nucleus > binds to DNA to affect gene transcription (rate of protein production)

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13
Q

What happens depending on the kind of steroid receptor that the ligand binds to?

A

The receptor can cause the protein production to increase or decrease

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14
Q

What are the known estrogen receptors?

A
  1. ERalpha
  2. ERbeta
  3. GPER1 (g-protein coupled receptor)
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15
Q

Where is a nuclear protein receptor TYPICALLY located?

A

In the cytosol of the neuron, where the ligand then bonds to it

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16
Q

What does phosphorylation mean?

A

Adding a phosphate

17
Q

What is kinase?

A

An enzyme that adds a phosphate group

18
Q

What are the characteristics that all G-protein coupled receptors have?

A
  1. they are the most diverse
  2. they typically take between 100-200 ms
  3. They are always embedded in the membrane
  4. they all have 7 transmembrane domains
19
Q

What are the three subunits of the G-protein coupled receptor?

A
  1. Alpha
  2. Beta
  3. Gamma
    + guanine diphosphate (GDP)
20
Q

What happens when a ligand binds to a G-protein coupled receptor’s active site?

A

The receptor’s tail binds to the G-protein and knocks off the GDP in favour of adding guanine triphosphate (GTP)
- the alpha subunit separates from beta and gamma subunits to become an active enzyme

21
Q

What is the whole basis of intracellular messaging?

A

Phosphorylation

- inactive protein > protein kinase > phosphorylated (active) protein > protein phosphatase (dephosphorylation)

22
Q

How long is the phosphorylated protein active for?

A

only temporarily (protein phosphatase is everywhere and deactivates the phosphorylated protein almost immediately)

23
Q

What are second messengers?

A

Anything that goes on to phosphorylate

24
Q

Describe the second messenger cascade from the bondng of a ligand onto a G-protein coupled receptor

A

mACh binds to active site > receptor attaches itself to subunits > alpha subunit cleaves and acts on adenylyl cyclase > adenylyl cyclase produces cyclic AMP (cAMP) > cAMP produces PKA (protein kinase A) > PKA can go on to activate a ligand-gated ion channel

25
Q

What are the two biggest functions of a G-protein coupled receptor?

A
  1. amplifies signal

2. increases signal duration

26
Q

Describe the PIP2 cascade

A

Alpha subunit acts on phospholipase C > PLC cleaves PIP2 > PIP2 becomes two second messengers:

a. a fat-soluble DAG (activates protein kinase C)
b. a water-soluble IP3 (activates a receptor on the smooth endoplasmic reticulum) > membrane becomes permeable to Ca2+

27
Q

Describe the Ca2+ cascade (or the CaMKII)

A

Ca2+ binds to calmodulin > calmodulin binds to CaMKII > CaMKII acts as a transcription factor (implicated in memory)

28
Q

What are the three second messenger cascades?

A

The G-protein coupled receptor cascade, the PIP2 cascade, and the calcium cascade

Neuropharmacology (18 decks)

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