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Neuropharmacology Final > Lecture 9: Neuropeptides And Hormones > Flashcards

Lecture 9: Neuropeptides And Hormones Flashcards

1
Q

What are peptide neurotransmitter’s composition?

A

Small proteins, made up of the 20 amino acids; joined by peptide bonds

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2
Q

Neuropeptide

A

Peptides that serve as neurotransmitters; can also serve as hormones

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3
Q

Neuropeptide synthesis 4 steps

A
  1. Neuropeptide are encoded by genes; “prepropeptides”; regulated like any other protein in the body
  2. Prepropepide mRNA trans locates to the ER, guided by a “signal peptide”
  3. Signal peptidase cleaves bond between the prepropeptide and signal peptide —> propeptide
  4. Propeptide is released from the ribosome that undergoes extensive posttranslational modification to become the active neuropeptide (cleavages and modifications at specific amino acid residues)
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4
Q

What are the 6 steps involved in the processing of POMC?

A
  1. The POMC gene encodes the propeptide for a number of active neuropeptides including ACTH, beta-endorphins, and melanocyte-stimulating hormone or MSH (Prepropeptide)
  2. The prepropeptide is translocated to the ER where it is translated into propeptide
  3. The propeptides are processed by prohormone convertases 1 and 2 (PC1 and PC2); stepwise reaction, cleaving certain dibasic residues (eg: Lys-Arg; Lys-Lys; Arg-Arg and Arg-Lys) —> smaller peptides with Lys and Arg at their N and C termini
  4. Carboxypeptidase E (CPE) and aminopeptidase remove these basic residues
  5. N terminal acetylation via N-acetylransferases can occur which regulates the activity of the neuropeptide (effect of acetylaton depends upon the particular peptide being processed)
  6. Amidation of glycine on C-terminus can occur via PAM
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5
Q

When is alpha-MSH activity increased?

A

Increased by N-terminal acetylation of POMC

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6
Q

What does N-terminal acetylation of POMC do?

A

Beta-endorphin activity is decreased

And alpha-MSH activity is increased

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7
Q

The specific neuropeptides synthesized from a prepropeptide gene depend on what? (POMC)

A

Upon the tissue because different tissues contain different prohormone convertases

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8
Q

For many prepropeptide genes, what does alternative mRNA splicing?

A

Can yield multiple gene products

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9
Q

What are are neuropeptides synthesized by?

A

Transcription, translation and posttranslational modifications in the cell body and axon (similar to any other protein)

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10
Q

Where are neuropeptides stored?

A

In large, dense core vesicles that are assembled in the Golgi network

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11
Q

How are the dense core vesicles containing neuropeptides transported?

A

Down the axon on microtubules

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12
Q

Where are dense core vesicles containing neuropeptides docked?

A

Outside of the active zone and are released upon large and sustained calcium entry into the cell (rapid train of action potentials)

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13
Q

Many neuropeptides are _____ with small ______ molecules

A

Co-localized

Neurotransmitter

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14
Q

What happens to neuropeptides under low stimulation conditions?

A

The small neurotransmitter vesicles will be mobilized and fuse with the membrane

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15
Q

What happens to neuropeptides under high stimulation conditions?

A

The dense core vesicles will be mobilized and fuse with the membrane

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16
Q

Within the striatum, what do D1 dopamine receptors do?

A

D1 dopamine receptor expressing striatonigral GABAergic neurons colocalize GABA with both Substance P and Dynorphin

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17
Q

Within the striatum, what do D2 dopamine receptors do?

A

D2 dopamine receptor expressing striatopallidal GABAergic neurons colocalize GABA with enkephalins

18
Q

What are the receptor types for neuropeptides?

A

The vast majority of cases, they are G protein coupled

19
Q

How do you get far reaching effects?

A

Disconnecting the receptor and neuropeptide localization in brain

20
Q

Neuropeptides bind with _____ affinity

A

Very high affinity (nM range vs small neurotransmitters which bind in muM range)

21
Q

What accounts for neuropeptides ability to interact with receptors?

A

The fact that they are flexible molecules

22
Q

Can neuropeptides cross the BBB?

A

NO! And therefore they are not suitable for treating brain dysfunction

23
Q

Opiates

A

Compounds purified from crude opium (opium poppies); specifically morphine, codeine and papaverine

24
Q

Opioids

A

Include any molecule exhibiting the properties of opiates, including synthetically produced molecules such as heroin (which is produced by altering the structure of morphine)

25
Q

Opioid peptides

A

Endogenously produced proteins synthesized in the CNS and periphery

26
Q

Which opioid peptide is the most potent?

A

Beta endorphins

27
Q

Which opioid peptide has slower degradation?

A

Beta endorphins

28
Q

What is the precursor of beta-endorphins?

A

POMC

29
Q

What are the receptor affinities of beta endorphins?

A

High mu
Medium delta
Low kappa

30
Q

What are the CNS influences of beta endorphins?

A

Neurons are NOT widely distributed but have long axons

31
Q

Enkephalins

A

Very potent opioid peptide

Broad effects

32
Q

What is the precursor for enkephalins?

A

Proenkephalin

33
Q

What are the receptor affinities of enkephalins?

A

High delta
Medium mu
Low kappa

34
Q

What are the CNS influences of enkephalins?

A

Widely distributed neuronal populations

Short axons

35
Q

Dynorphins

A

Least potent opioid peptide

Adversive effects

36
Q

What is the precursor for dynorphins?

A

Prodynorphins

37
Q

What are the receptor affinities of dynorphins?

A

High kappa
Medium delta
Low mu

38
Q

What are the CNS influences of dynorphins?

A

Limited distribution

Long axons

39
Q

Nociceptin

A

Formerly orphanin
identified opioid peptide in 1995
Binds ORL-1 receptor
Has HYPER-algesic effects

40
Q

Endomorphin

A

Has high affinity for mu receptor

41
Q

Opioid distribution in the brain is what? What are they all prevalent in?

A

Varies by peptide in the brain

All are prevalent in pain and reward pathways

42
Q

Distribution of opioid peptide producing neurons

A

Distributed throughout the CNS

Heavily integrated in pain pathways and dopaminergic reward pathways

Neuropharmacology Final (1 decks)

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