Neuropeptides!
What are Neuropeptides?
More than 100 different Neuropeptides so far identified in the
mammalian brain (90 genes encode precursors)
Neuropeptides are small protein-like molecules (3 – 30 amino acids long)
synthesised from larger precursors and used by neurones to communicate
with each other. Pre-propeptides are processed to give mature functional
peptides.
Neuropeptide signalling probably established before small molecule
transmitters and used widely by sea anemones, coral, jelly fish, Hydra.
Yeast signalling uses factors which are peptide-like molecules.
Some Neuropeptides act as Neurohormones produced in the
hypothalamus and act in peripheral tissues eg oxytocin and vasopressin -
some are also found and act in the GI tract (eg CCK) and some might be
neuronal only. Most are not exclusive to neurones/ the nervous system.
Neuropeptide actions:
Neuropeptides are expressed and released by neurones, and mediate or
modulate neuronal communication by acting
on cell surface receptors (GPCRs)
Neuropeptides act as neuronal signaling molecules, influencing particular
brain functions such as analgesia, reward, food intake, plasticity events
(learning and memory). Don’t mediate fast transmission/ signalling across
synapses like GABA, but are involved in more complex, modulatory CNS
functions.
Basic Properties of Neuropeptides:
Synthesised as a large precursor molecule at the cell soma (unlike SMTs
which have local synthesis) and transported to release sites in dense core
vesicles – replenished by further synthesis at soma (no
reuptake/recycling ability of SMTs, which can be taken up by glial
cells/nerve terminals and recycled).
Slow postsynaptic effects
Actions terminated by extracellular proteases or by diffusion
Co-released with classical neurotransmitters – stimulation of a given
synapse triggers fast release of primary NT e.g. glutamate, and then
, slower secondary release of
neuropeptide, which acts to
modulate local responses.
Can trigger complex co-
ordinated behaviours
Actions do not require point-
to-point synaptic connections
– can be released in different
parts of the cell and act
generally rather than in a local
area.
Schematic of the principle
intracellular pathway:
Synthesis within cell soma in
ribosomes, processing and trafficking in trans-Golgi network, processing
during transport along axon to nerve terminal. Processed from large
precursors to final functional neuropeptide. Stored in dense core vesicles
ready for secretion.
Differences between classical neurotransmitters and
neuropeptides:
Present at much lower concentrations in vesicles (~10mM compared with
100mM) than SMTs, which occupy vesicles at concentrations over 100Mm.
Much higher affinity for receptors (nM – mM; compared with mM – mM)
– this is due to their lower concentration. SMTs packaged at high
concentrations are released in high concentrations in the locality of the
receptor, therefore only need to have modest affinity for receptors.
Whereas neuropeptides are released more diffusely, so receptor must be
much more sensitive.
Synthesised from precursors, used only once – released, broken down,
no recycling/reuptake capability within nerve terminal.
Release requires a more intense stimulus and initially more Calcium
entry but ultimately neuropeptide release requires lower
concentrations of Ca2+ compared to SMVs.
Neuropeptides and classical neurotransmitters can be released
from different parts of the nerve terminal:
What are Neuropeptides?
More than 100 different Neuropeptides so far identified in the
mammalian brain (90 genes encode precursors)
Neuropeptides are small protein-like molecules (3 – 30 amino acids long)
synthesised from larger precursors and used by neurones to communicate
with each other. Pre-propeptides are processed to give mature functional
peptides.
Neuropeptide signalling probably established before small molecule
transmitters and used widely by sea anemones, coral, jelly fish, Hydra.
Yeast signalling uses factors which are peptide-like molecules.
Some Neuropeptides act as Neurohormones produced in the
hypothalamus and act in peripheral tissues eg oxytocin and vasopressin -
some are also found and act in the GI tract (eg CCK) and some might be
neuronal only. Most are not exclusive to neurones/ the nervous system.
Neuropeptide actions:
Neuropeptides are expressed and released by neurones, and mediate or
modulate neuronal communication by acting
on cell surface receptors (GPCRs)
Neuropeptides act as neuronal signaling molecules, influencing particular
brain functions such as analgesia, reward, food intake, plasticity events
(learning and memory). Don’t mediate fast transmission/ signalling across
synapses like GABA, but are involved in more complex, modulatory CNS
functions.
Basic Properties of Neuropeptides:
Synthesised as a large precursor molecule at the cell soma (unlike SMTs
which have local synthesis) and transported to release sites in dense core
vesicles – replenished by further synthesis at soma (no
reuptake/recycling ability of SMTs, which can be taken up by glial
cells/nerve terminals and recycled).
Slow postsynaptic effects
Actions terminated by extracellular proteases or by diffusion
Co-released with classical neurotransmitters – stimulation of a given
synapse triggers fast release of primary NT e.g. glutamate, and then
, slower secondary release of
neuropeptide, which acts to
modulate local responses.
Can trigger complex co-
ordinated behaviours
Actions do not require point-
to-point synaptic connections
– can be released in different
parts of the cell and act
generally rather than in a local
area.
Schematic of the principle
intracellular pathway:
Synthesis within cell soma in
ribosomes, processing and trafficking in trans-Golgi network, processing
during transport along axon to nerve terminal. Processed from large
precursors to final functional neuropeptide. Stored in dense core vesicles
ready for secretion.
Differences between classical neurotransmitters and
neuropeptides:
Present at much lower concentrations in vesicles (~10mM compared with
100mM) than SMTs, which occupy vesicles at concentrations over 100Mm.
Much higher affinity for receptors (nM – mM; compared with mM – mM)
– this is due to their lower concentration. SMTs packaged at high
concentrations are released in high concentrations in the locality of the
receptor, therefore only need to have modest affinity for receptors.
Whereas neuropeptides are released more diffusely, so receptor must be
much more sensitive.
Synthesised from precursors, used only once – released, broken down,
no recycling/reuptake capability within nerve terminal.
Release requires a more intense stimulus and initially more Calcium
entry but ultimately neuropeptide release requires lower
concentrations of Ca2+ compared to SMVs.
Neuropeptides and classical neurotransmitters can be released
from different parts of the nerve terminal:
