Neuropeptides Flashcards
Mechanism of release of neuropeptides and examples of neuropeptides
They are not necessarily released at the synaptic cleft. They will diffuse and act at GPCRs. As it is not released at the synaptic cleft, they can affect surrounding cells. Vesciles that release them are significantly larger and recycled slower.
Opioids: enkephalins and endorphins.
Peptide hormones: oxytocin, substance P, cholecystokinin, vasopressin, neuropeptide Y.
Hypothalamic releasing hormones: GnRH (gonadotropin-), TRH (thyrotropin-), CRH (corticotropin-)
Upon release they are metabolised, no reuptake.
how Neuropeptide are formed (cleaving pathway)
Look at image to be more clear. Prepropeptide cleaved by signal peptidases, removing the signal peptide region.
Propeptide cleaved by endopeptidases and exopiptases to form the peptides.
PTMs then add functional groups to the peptides where they are then in their final form (e.g., adding NH2 or phosphate group, etc…)
Neuropeptides functions and types of communications
Autocrine (interacts with cell its released from), paracrine (acts at nearby cells), and endocrine (acts at cells far away from the blood).
Roles in analgesia, food intake, learning/memory, metabolism, reproduction, and social behaviours.
Neuropeptides vs neurotransmitters
Synthesis: NPs formed in rough ER, NTs synthesised in the cytosol
Conc: NPs formed in low concs, NTs formed in high concs.
Location: NPs found all over neuron, NTs found in axon terminal.
Storage: NPs in large dense-core vesicles (LDCVs), NTs in small secretory vesicles (SSVs).
MW: NPs high, NTs low
Time of activity and response duration: NPs slow, NTs fast
Release time: NPs take longer before release, NTs quickly released.
[Ca] release: NPs at low [Ca], NTs at high [Ca]
Potency: NPs high, NTs low
Large dense core vesicles contents and synthesis
70-200nm
Can contain NPs, growth factors, NTs, and hormones.
They are synthesised in the cell body and then transported to the terminals. They are released from the neurone distant from the active zone. They are released following a train of APs.
Tahcykinin (TAC) family structure
Largest family of NPs, e.g., substance P, neuropeptide Y, etc…
All have a conserved COOH terminal sequence, but have varying N-terminals.
NPY (TAC family) actions
NPY is a 36-AA NP. Acts in CNS and ANS. Acts predominantly at Gai and some Gaq receptors. Can have appetising or anorectic function depending on GPCR type stimulated.
In ANS is a vasoconstrictor and grows fat tissue
In CNS increases food intake, storage of energy as fat, role in decreasing anxiety and stress, and effects circadian rhythm and role in pathology of epilepsy.
Studies found it modulated glutamate induced Ca2+ response. decreased [Ca] following NPY application
Substance P (TAC family) effects, receptor, effect of capsaicin, and antagonist used
A 11-AA long NP. Binds to NK1R
Substance P acts at NK1, antagonist produced for chemo nausea: aprepitant.
Capsaicin has been found to release substance P, which can then cause it to quickly deplete (part of the desensitisation mechanism)
Substance P is a potent vasodilator. Dependent on NO.
Also promotes wound healing.
BDNF
Mediates neurogenesis. Increases synaptic plasticity.
Induces growth, survival, and differentiation of neurones.
It was found to stimulate neuronal activity.
Somatostatin
2 main isoforms: 14 or 28 AA long.
14 primarily acts in brain, 28 primarily in GIT.
Has roles in motor activity, sleep, sensory processes, and cognitive processes.
Involved in pathology of AD, PD, depression and schizophrenia
Acts at SST GPCRs. Activation of SST associated with decreased hormone secretion, angiogenesis, cell proliferation, and cell growth. Increased apoptosis and cell cycle arrest
A study found stimulation of somatostatin signalling in mice induced anxiety.
