Neuropeptides Flashcards
How do NTs and neuropeptides differ in the following ways:
- Speed
- Distance
- Receptors
- 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
How do they types of vesicles differ between NTs & NPs?
NTs = have clear synaptic vesicles
NPs = have dense core vesicles
What are NTs split into?
Amines & amino acids
What are neuropeptides split into?
- Opiodpeptides
- Pepide hormones
- Hypothalamic Releasing Hormones
Name some amine NTs:
- Quaternary amines = ACh
Monoamines are split into:
- Catecholamines = Epinephrine (EPI) & Norepinephrine (NE) & Dopamine (DA)
- Indoleamines = Serotonin (5-HT) & Melatonin
Name some amino acid NTs:
- Gamma-aminobutyric acid (GABA)
- Glutamate (GLU)
- Glycines
- Histamine (HIST)
Name some opiodpeptide NPs:
- Enkephalins (ENK)
- Endorphins (END)
Name some peptide hormone NPs:
- Oxytocin (Oxy)
- Substance P
- Cholecystokinin (CCK)
- Vasopressin (ADH)
- Neuropeptide Y (NPY)
Name some hypothalamic releasing hormones (NPs):
- GnRH (Gonadotropin-releasing hormone)
- TRH (Thyrotropin-releasing hormone)
- CRH (Corticotropin-releasing hormone)
How are NTs made?
In a cascade manner - using a precursor such s tyrosine
How are NPs synthesised?
- 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
What are neuropeptides? (Define)
NPs are small protein like molecules (peptides) used by neurons to communicate w each other
(Autocrine/paracrine/endocrine signalling used)
What is autocirne signalling?
Peptide is produced in one cell & signals to own source of production
(Cell targets itself)
What is paracrine signalling?
Peptides released by one cell & signal to nearby cell
What is endocrine signalling?
Cell targets a distant cell thru the bloodstream
What happens to a NP once it has been secreted?
Neuronal signalling molecules not recycled back into cell once secreted
Unlike glutamate, dopamine, serotonin etc
What do neuropeptides play a role in?
Responsible for brain function:
- Analgesia
- Food intake
- Learning & memory
- Metabolism, reproduction
- Social behaviours
Name the NPs responsible for these brain functions:
- Analgesia
- Food intake
- Learning & memory
- Metabolism, reproduction
- Social behaviours
- Analgesia = Neueropeptide Y (NPY)
- Food intake = Cholecystokinin
- Learning & memory = Tachykinins (sub P, neurokinin)
- Metabolism, reproduction = Arginine vasopressin (AVP)
- Social behaviours = Corticotropin releasing factor (CRF)
How does the synthesis of NTs and NPs differ?
Neurpeptides = synthesised in RER & Golgi apparatus
Neurotransmitters = synthesised in cytosol of presynaptic neurons terminals
How does the concentration of NTs and NPs differ?
Neuropeptides = synthesised in low concs
Neurotransmitters = synthesised in high concs
How does the location of NTs and NPs differ?
Neuropeptides = found all over neuron
Neurotransmitters = only found in the axon terminals of presynaptic neurons
How does the storage of NTs and NPs differ?
Neuropeptide = stored in large dense-cove vesicles (LDCVs)
Neuotransmitters = stored in small secretory vesicles (SSVs)
How does the molecular weight of NTs and NPs differ?
Neuropeptides = have high molecular weight
Neurotransmitters = have low molecular weight
How does the activity of NTs and NPs differ?
Neuropeptides = are slow-acting
Neurotransmitters = are fast-acting
How does the response of NTs and NPs differ?
Neuropeptides = produce a slow response
Neurotransmitters = produce acute response
How does the duration of NTs and NPs differ?
Neuropeptides = produce a prolonged action
Neurotransmitters = trigger short-term response
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
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
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
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
How does the potency of NTs and NPs differ?
Neuropeptides = ~1000 times more potent than NTs
Neurotransmitters = less potent compared to NPs
Give examples of NTs & NPs:
Neuropeptides = Oxytocin, vasopressin, insulin, neuropeptide Y
Neurotransmitters = ACh, dopamine, serotonin, glutamate & histamine
Where are NTs synthesised vs NPs?
NT = synthesised in neurone terminals
NP = synthesis in cell body, not in terminal
What are NTs synthesised from vs NPs?
NT = Synthesis from precursor by enzymes
NP = cleaved from larger precursor protein
How do the size of NP vs NT vesicles differ?
NT = small electron translucent storage (up to 45nm)
NP = only stored in LDCVs (>70nm)
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+
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
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)
How are NTs vs NPs removed?
NT = metabolised by specific enzymes, transporter uptake
NP = enzymes lack specificity, no re-uptake
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
How big are large dense core vesicles?
70-200nm
What do large dense core vesicles contain?
Neuropeptides, growth factors, classical NTs and hormones
Where are large dense core vesicles synthesised?
Synthesised in cell body
Where are large dense core vesicles transported to?
Transported to terminals
Are large dense core vesicles recycled?
No - there is no recycling of LDCVs
How do the numbers of large dense core vesicles compare to NT vesicles?
Fewer LDCVs than small electron translucent vesicles
Where are large dense core vesicles located?
Located distance from the active zone
How are large dense core vesicles released?
Released w high freq trains of APs
What do large dense core vesicles provide?
They provide diffuse, slow neuromodulatory actions
What are some examples of NPs that originate from hypothalamic releasing hormones?
- Thyrotropin-releasin hormone
- Somatostatin
- Neuropeptide Y (NPY)
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
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
What are some examples of NPs that originate from other tissues?
- Angiotensin-II
- Bradykinin
- Carnosine
- Sleep peptides
- Calcitonin
What are Tachykinins (TAC)?
The largest families of neuropeptides
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)
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)
What is the action of substance P & what does it act on?
Substance P inhibits synaptic neuronal activity
It acts on the NK1R receptor
What is was the first NK1R antagonist & what is its action?
Aprepitant –> used to treat chemo induced nausea & vomiting (CINV)
How does aprepitant work?
It blocks the binding of Substance P to NK1R receptor which induces nausea
What is the structure or neuropeptide Y & where is it found?
- A 36 amino acid
- Acts as a NT in the brain & ANS
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
What is the role of ANS neuropeptide Y?
- Produced mainly by neruons of the sympathetic NS
- Strong vasoconstrictor
- Growth of fat tissue
What are the neuropeptide Y (NPY) receptors?
NPY1R, Y2R, Y4R, Y5R, Y6R
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
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)
Which neuropeptides are feeding stimulators?
NPY1R & NPY5R (appetizer)
Which neuropeptides are appetite inhibitors?
NPY2R & NPY4R (anorectic function)
Was a couple slides on NPY cascade but I didn’t get notes on them - meg if u did pls add them xx
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What family does substance P belong to?
The tachykinin (TAC) neuropeptide family
What is an undecapeptide & give an example?
A petite composed of a chain of 11 AA residues
Finish from substance P slide
