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Disease in the brain > Neuropeptides > Flashcards

Neuropeptides Flashcards

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1
Q

How do NTs and neuropeptides differ in the following ways:

  • Speed
  • Distance
  • Receptors
A
  • NTs = fast vesicle recycling & NPs = slow vesicle recycling
  • NTs = ultra short distance (nanometers) & NPs = local diffusion (micrometers)
  • NTs = ionotropic receptors & NPs = G-protein coupled receptors
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2
Q

How do they types of vesicles differ between NTs & NPs?

A

NTs = have clear synaptic vesicles

NPs = have dense core vesicles

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3
Q

What are NTs split into?

A

Amines & amino acids

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4
Q

What are neuropeptides split into?

A
  • Opiodpeptides
  • Pepide hormones
  • Hypothalamic Releasing Hormones
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5
Q

Name some amine NTs:

A
  • Quaternary amines = ACh

Monoamines are split into:
- Catecholamines = Epinephrine (EPI) & Norepinephrine (NE) & Dopamine (DA)

  • Indoleamines = Serotonin (5-HT) & Melatonin
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6
Q

Name some amino acid NTs:

A
  • Gamma-aminobutyric acid (GABA)
  • Glutamate (GLU)
  • Glycines
  • Histamine (HIST)
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7
Q

Name some opiodpeptide NPs:

A
  • Enkephalins (ENK)
  • Endorphins (END)
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8
Q

Name some peptide hormone NPs:

A
  • Oxytocin (Oxy)
  • Substance P
  • Cholecystokinin (CCK)
  • Vasopressin (ADH)
  • Neuropeptide Y (NPY)
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9
Q

Name some hypothalamic releasing hormones (NPs):

A
  • GnRH (Gonadotropin-releasing hormone)
  • TRH (Thyrotropin-releasing hormone)
  • CRH (Corticotropin-releasing hormone)
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10
Q

How are NTs made?

A

In a cascade manner - using a precursor such s tyrosine

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11
Q

How are NPs synthesised?

A
  • Starts with a prepropeptide –> this cont a large seq of amino acids
  • Cleavage by signal peptidases –> makes a propeptide
  • Cleavage by endopeptidases & exopeptidases –> makes a peptide
  • Posttranslational modifications –> makes a functional peptide
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12
Q

What are neuropeptides? (Define)

A

NPs are small protein like molecules (peptides) used by neurons to communicate w each other

(Autocrine/paracrine/endocrine signalling used)

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13
Q

What is autocirne signalling?

A

Peptide is produced in one cell & signals to own source of production

(Cell targets itself)

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14
Q

What is paracrine signalling?

A

Peptides released by one cell & signal to nearby cell

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15
Q

What is endocrine signalling?

A

Cell targets a distant cell thru the bloodstream

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16
Q

What happens to a NP once it has been secreted?

A

Neuronal signalling molecules not recycled back into cell once secreted

Unlike glutamate, dopamine, serotonin etc

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17
Q

What do neuropeptides play a role in?

A

Responsible for brain function:
- Analgesia
- Food intake
- Learning & memory
- Metabolism, reproduction
- Social behaviours

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18
Q

Name the NPs responsible for these brain functions:
- Analgesia
- Food intake
- Learning & memory
- Metabolism, reproduction
- Social behaviours

A
  • Analgesia = Neueropeptide Y (NPY)
  • Food intake = Cholecystokinin
  • Learning & memory = Tachykinins (sub P, neurokinin)
  • Metabolism, reproduction = Arginine vasopressin (AVP)
  • Social behaviours = Corticotropin releasing factor (CRF)
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19
Q

How does the synthesis of NTs and NPs differ?

A

Neurpeptides = synthesised in RER & Golgi apparatus

Neurotransmitters = synthesised in cytosol of presynaptic neurons terminals

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20
Q

How does the concentration of NTs and NPs differ?

A

Neuropeptides = synthesised in low concs

Neurotransmitters = synthesised in high concs

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21
Q

How does the location of NTs and NPs differ?

A

Neuropeptides = found all over neuron

Neurotransmitters = only found in the axon terminals of presynaptic neurons

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22
Q

How does the storage of NTs and NPs differ?

A

Neuropeptide = stored in large dense-cove vesicles (LDCVs)

Neuotransmitters = stored in small secretory vesicles (SSVs)

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23
Q

How does the molecular weight of NTs and NPs differ?

A

Neuropeptides = have high molecular weight

Neurotransmitters = have low molecular weight

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24
Q

How does the activity of NTs and NPs differ?

A

Neuropeptides = are slow-acting

Neurotransmitters = are fast-acting

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25
Q

How does the response of NTs and NPs differ?

A

Neuropeptides = produce a slow response

Neurotransmitters = produce acute response

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26
Q

How does the duration of NTs and NPs differ?

A

Neuropeptides = produce a prolonged action

Neurotransmitters = trigger short-term response

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27
Q

How does the release of NTs and NPs differ?

A

Neuropeptides = axonal streaming of NTs occurs in few cm/day

Neurotransmitters = release within few milliseconds upon an arrival of an AP

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28
Q

What are NPs vs NTs released with?

A

Neuropeptides = released to the synaptic cleft / surroundings along w another NT

Neurotransmitters = are released individually depending on the AP

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29
Q

How does the cytosolic Ca2+ conc differ in NTs and NPs?

A

Neuropeptides = are released at low cytosolic Ca2+ concs

Neurotransmitters = are released at high cytosolic Ca2+ concs

30
Q

How does the site of action differ in NTs vs NPs?

A

Neuropeptides = have a different site of action than their origin - diffusion

Neurotransmitters = are released in direct apposition to their target cells

31
Q

How does the potency of NTs and NPs differ?

A

Neuropeptides = ~1000 times more potent than NTs

Neurotransmitters = less potent compared to NPs

32
Q

Give examples of NTs & NPs:

A

Neuropeptides = Oxytocin, vasopressin, insulin, neuropeptide Y

Neurotransmitters = ACh, dopamine, serotonin, glutamate & histamine

33
Q

Where are NTs synthesised vs NPs?

A

NT = synthesised in neurone terminals

NP = synthesis in cell body, not in terminal

34
Q

What are NTs synthesised from vs NPs?

A

NT = Synthesis from precursor by enzymes

NP = cleaved from larger precursor protein

35
Q

How do the size of NP vs NT vesicles differ?

A

NT = small electron translucent storage (up to 45nm)

NP = only stored in LDCVs (>70nm)

36
Q

How do NPs and NTs differ in their Ca2+ dependent release?

A

NT = Ca2+ & K+ dependent release –> released by low and high freq stimulation N/L-type Ca2+ - classical

NP = Ca2+ & K+ dependent release –> released by high freq stimulation or firing L-type Ca2+

37
Q

What do NT vs NP act on?

A

NT = act on receptor proteins - inotropic and metabotropic

NP = Activate second messenger - none are coupled to ion channels

38
Q

How consistent are NPs vs NTs across species?

A

NT = similar across species (excitatory or inhibitors NT)

NP = species variation in aa seq (slow neuromodular & many family of peptides)

39
Q

How are NTs vs NPs removed?

A

NT = metabolised by specific enzymes, transporter uptake

NP = enzymes lack specificity, no re-uptake

40
Q

How do the proportions of NPs vary across species?

A

Proportion & exact neuropeptides present in each nerve vary across species & may change w disease or developmental stage

41
Q

How big are large dense core vesicles?

A

70-200nm

42
Q

What do large dense core vesicles contain?

A

Neuropeptides, growth factors, classical NTs and hormones

43
Q

Where are large dense core vesicles synthesised?

A

Synthesised in cell body

44
Q

Where are large dense core vesicles transported to?

A

Transported to terminals

45
Q

Are large dense core vesicles recycled?

A

No - there is no recycling of LDCVs

46
Q

How do the numbers of large dense core vesicles compare to NT vesicles?

A

Fewer LDCVs than small electron translucent vesicles

47
Q

Where are large dense core vesicles located?

A

Located distance from the active zone

48
Q

How are large dense core vesicles released?

A

Released w high freq trains of APs

49
Q

What do large dense core vesicles provide?

A

They provide diffuse, slow neuromodulatory actions

50
Q

What are some examples of NPs that originate from hypothalamic releasing hormones?

A
  • Thyrotropin-releasin hormone
  • Somatostatin
  • Neuropeptide Y (NPY)
51
Q

What are some examples of NPs that originate from pituitary peptides?

A
  • Adrenocorticotropic hormone (ACTH)
  • Beta-endorphin
  • Alpha-melanocyte-stimulating hormone (alpha-MSH)
  • Thyroid stimulating hormone (TSH)
  • Vasopressing
  • Oxytocin
52
Q

What are some example of NPs that originate from peptides acting on gut & brain?

A
  • Leucin enkephalin
  • Methionine enkephalin
  • Substance P
  • Gastrin
  • Nerve GF
  • Brain derived neurotropic factors (BDNF)
  • Neurotrensin
  • Insulin
  • Glucagon
53
Q

What are some examples of NPs that originate from other tissues?

A
  • Angiotensin-II
  • Bradykinin
  • Carnosine
  • Sleep peptides
  • Calcitonin
54
Q

What are Tachykinins (TAC)?

A

The largest families of neuropeptides

55
Q

What is the characteristic of Tachykinins (TAC)?

A

Converved COOH-terminal seq but varying N-terminal

All have -Phe-X-Gly-Leu-Met-NH2, X hydrophobic AA –> receptor activation

(e.g. sub p & neuropeptide Y)

56
Q

How are NTs & NPs structurally different?

A

Comparing AAs to NTs for example –> structures like DA are v small compared to prepropeptides (e.g. sub P)

57
Q

What is the action of substance P & what does it act on?

A

Substance P inhibits synaptic neuronal activity

It acts on the NK1R receptor

58
Q

What is was the first NK1R antagonist & what is its action?

A

Aprepitant –> used to treat chemo induced nausea & vomiting (CINV)

59
Q

How does aprepitant work?

A

It blocks the binding of Substance P to NK1R receptor which induces nausea

60
Q

What is the structure or neuropeptide Y & where is it found?

A
  • A 36 amino acid
  • Acts as a NT in the brain & ANS
61
Q

What are the actions of brain Neuropeptide Y?

A
  • Produced mainly by hypothalamus
  • Inc food intake
  • Inc storage of energy as fat
  • Dec anxiety & stress, voluntary alcohol intake, BP, pain perception
  • Affecting the circadian rhythm

-Controlling epileptic seizures

62
Q

What is the role of ANS neuropeptide Y?

A
  • Produced mainly by neruons of the sympathetic NS
  • Strong vasoconstrictor
  • Growth of fat tissue
63
Q

What are the neuropeptide Y (NPY) receptors?

A

NPY1R, Y2R, Y4R, Y5R, Y6R

64
Q

What sort of receptors are the NPY receptors?

A

G-protein coupled receptors (GPCR), Gi proteins, which leads to the inhibition of adenylate cyclase & finally inhibittion of cAMP accumulation or PLC activation

65
Q

What are NPY2R and Y4R also coupled with?

What does this coupling do?

A

As well as being coupled with Gi proteins:

Also couple to Gq protein increasing inositol 1,4,5-phosphate (IP3) production via the activation of the phospholipase C-beta (PLC)

66
Q

Which neuropeptides are feeding stimulators?

A

NPY1R & NPY5R (appetizer)

67
Q

Which neuropeptides are appetite inhibitors?

A

NPY2R & NPY4R (anorectic function)

68
Q

Was a couple slides on NPY cascade but I didn’t get notes on them - meg if u did pls add them xx

A

h

69
Q

What family does substance P belong to?

A

The tachykinin (TAC) neuropeptide family

70
Q

What is an undecapeptide & give an example?

A

A petite composed of a chain of 11 AA residues

71
Q

Finish from substance P slide

A

Disease in the brain (22 decks)

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