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Neuropeptides Flashcards

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
How does the response of NTs and NPs differ?
Neuropeptides = produce a slow response Neurotransmitters = produce acute response
26
How does the duration of NTs and NPs differ?
Neuropeptides = produce a prolonged action Neurotransmitters = trigger short-term response
27
How does the release of NTs and NPs differ?
Neuropeptides = axonal streaming of NTs occurs in few cm/day Neurotransmitters = release within few milliseconds upon an arrival of an AP
28
What are NPs vs NTs released with?
Neuropeptides = released to the synaptic cleft / surroundings along w another NT Neurotransmitters = are released individually depending on the AP
29
How does the cytosolic Ca2+ conc differ in NTs and NPs?
Neuropeptides = are released at low cytosolic Ca2+ concs Neurotransmitters = are released at high cytosolic Ca2+ concs
30
How does the site of action differ in NTs vs NPs?
Neuropeptides = have a different site of action than their origin - diffusion Neurotransmitters = are released in direct apposition to their target cells
31
How does the potency of NTs and NPs differ?
Neuropeptides = ~1000 times more potent than NTs Neurotransmitters = less potent compared to NPs
32
Give examples of NTs & NPs:
Neuropeptides = Oxytocin, vasopressin, insulin, neuropeptide Y Neurotransmitters = ACh, dopamine, serotonin, glutamate & histamine
33
Where are NTs synthesised vs NPs?
NT = synthesised in neurone terminals NP = synthesis in cell body, not in terminal
34
What are NTs synthesised from vs NPs?
NT = Synthesis from precursor by enzymes NP = cleaved from larger precursor protein
35
How do the size of NP vs NT vesicles differ?
NT = small electron translucent storage (up to 45nm) NP = only stored in LDCVs (>70nm)
36
How do NPs and NTs differ in their Ca2+ dependent release?
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
What do NT vs NP act on?
NT = act on receptor proteins - inotropic and metabotropic NP = Activate second messenger - none are coupled to ion channels
38
How consistent are NPs vs NTs across species?
NT = similar across species (excitatory or inhibitors NT) NP = species variation in aa seq (slow neuromodular & many family of peptides)
39
How are NTs vs NPs removed?
NT = metabolised by specific enzymes, transporter uptake NP = enzymes lack specificity, no re-uptake
40
How do the proportions of NPs vary across species?
Proportion & exact neuropeptides present in each nerve vary across species & may change w disease or developmental stage
41
How big are large dense core vesicles?
70-200nm
42
What do large dense core vesicles contain?
Neuropeptides, growth factors, classical NTs and hormones
43
Where are large dense core vesicles synthesised?
Synthesised in cell body
44
Where are large dense core vesicles transported to?
Transported to terminals
45
Are large dense core vesicles recycled?
No - there is no recycling of LDCVs
46
How do the numbers of large dense core vesicles compare to NT vesicles?
Fewer LDCVs than small electron translucent vesicles
47
Where are large dense core vesicles located?
Located distance from the active zone
48
How are large dense core vesicles released?
Released w high freq trains of APs
49
What do large dense core vesicles provide?
They provide diffuse, slow neuromodulatory actions
50
What are some examples of NPs that originate from hypothalamic releasing hormones?
- Thyrotropin-releasin hormone - Somatostatin - Neuropeptide Y (NPY)
51
What are some examples of NPs that originate from pituitary peptides?
- Adrenocorticotropic hormone (ACTH) - Beta-endorphin - Alpha-melanocyte-stimulating hormone (alpha-MSH) - Thyroid stimulating hormone (TSH) - Vasopressing - Oxytocin
52
What are some example of NPs that originate from peptides acting on gut & brain?
- Leucin enkephalin - Methionine enkephalin - Substance P - Gastrin - Nerve GF - Brain derived neurotropic factors (BDNF) - Neurotrensin - Insulin - Glucagon
53
What are some examples of NPs that originate from other tissues?
- Angiotensin-II - Bradykinin - Carnosine - Sleep peptides - Calcitonin
54
What are Tachykinins (TAC)?
The largest families of neuropeptides
55
What is the characteristic of Tachykinins (TAC)?
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
How are NTs & NPs structurally different?
Comparing AAs to NTs for example --> structures like DA are v small compared to prepropeptides (e.g. sub P)
57
What is the action of substance P & what does it act on?
Substance P inhibits synaptic neuronal activity It acts on the NK1R receptor
58
What is was the first NK1R antagonist & what is its action?
Aprepitant --> used to treat chemo induced nausea & vomiting (CINV)
59
How does aprepitant work?
It blocks the binding of Substance P to NK1R receptor which induces nausea
60
What is the structure or neuropeptide Y & where is it found?
- A 36 amino acid - Acts as a NT in the brain & ANS
61
What are the actions of brain Neuropeptide Y?
- 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
What is the role of ANS neuropeptide Y?
- Produced mainly by neruons of the sympathetic NS - Strong vasoconstrictor - Growth of fat tissue
63
What are the neuropeptide Y (NPY) receptors?
NPY1R, Y2R, Y4R, Y5R, Y6R
64
What sort of receptors are the NPY receptors?
G-protein coupled receptors (GPCR), Gi proteins, which leads to the inhibition of adenylate cyclase & finally inhibittion of cAMP accumulation or PLC activation
65
What are NPY2R and Y4R also coupled with? What does this coupling do?
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
Which neuropeptides are feeding stimulators?
NPY1R & NPY5R (appetizer)
67
Which neuropeptides are appetite inhibitors?
NPY2R & NPY4R (anorectic function)
68
Was a couple slides on NPY cascade but I didn't get notes on them - meg if u did pls add them xx
h
69
What family does substance P belong to?
The tachykinin (TAC) neuropeptide family
70
What is an undecapeptide & give an example?
A petite composed of a chain of 11 AA residues
71
Finish from substance P slide

Disease in the brain (22 decks)

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