Neuropeptides

Neuropeptides

What are neuropeptides
1. Small protein like molecules
  1. 3-30 aa
2. Synthesised from larger precursors
  1. At least 90 aa
  2. Removal of signal sequence, cleavage events and disulphide bond formation
  3. In some cases a single precursor molecular can give rise to multiple bioactive peptides
3. Used by neurones to communicate with each other
4. More than 100 different neuropeptides identified in the mammalian brain
5. Expressed and released by neurones
6. Mediate or modulate neuronal communication by acting on cell surface receptors e.g. GPCRs
7. Act as neuronal signalling molecules, influencing particular brain functions e.g. learning and memory
Properties
1. Synthesised as a large precursor molecule at the cell soma
2. Transported to release sites in dense core vesicles
3. Slow postsynaptic effects
4. Actions terminated by extracellular proteases or by diffusion
5. Can trigger complex coordinated behaviours
6. Actions do not require point to point synaptic connections
Differences between NT and neuropeptides
1. Much lower concentrations in vesicles
  1. About 10mM compared with 100 mM
2. Much higher affinity for receptors
3. Synthesised from precursors and only used once
4. Released by lower concentraton of Ca2+ away from point of entry
  1. Neuropeptides and NT can be released form different parts of the nerve terminal
Major neuropeptides of the mammalian brain
1. Substance P
  1. Sensory and pain
  2. Released from the terminals of specific sensory nerves
  3. Found in the brain and spinal cord and is associated with inflammatory processes and pain
  4. Coexists with the excitatory NT glutamate in primary afferents that respond to painful stimulation
  5. Also associated with anxiety, stress, neurogenesis and nausea
  6. Signalling mediated through Neurokinin 1 (NK1) receptors
2. Neurotensin
  1. Regulation of release of other peptides
3. Oxytocin
4. Vasopressin
5. Neuropeptide Y
6. alpha-endorphin
7. Met-enkephalin
Opoid peptides
1. Two functional pentapeptides identified
  1. Enkephalins
2. Three additional longer peptides later identified
  1. Endorphins
3. Enkephalins and endorphins found throughout the brain but are not co-localised in the same neurones
Degredation
1. Enzymatic
  1. Aminopeptidase
  2. Neprilysin
  3. Insulin degrading enzyme
  4. Angiotensin converting enzyme

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	Created by zambrella almost 11 years ago