Tuesday, March 18, 2014 CC-BY-NC

Maintainer: admin

1Neuropeptide synthesis

1.1neropeptide versus classical transmitters

  • while there are ~10 classical transmitters, there are over 100 neuropeptides
  • neuropeptides ; made from protein precursors encoded by genes
  • classical transmitter: made by enzymes in cytosol
    • except dopamine b-hydroxylase in vesicles
  • neuropeptide in dense-cored vesicles (regulated secretory vesicles) that need to be made.
  • classical transmitter in synaptic vesicles that can be reused.
  • while neuron have one classical transmitter, they can have multiple neuropepties

1.2Structure and process

  • neureptide precursor

    • cleavage sites
    • glycine for amidation : to protect it from degradation
    • a signal sequence for transport to ER, but so far not well-defined
  • as precursor so that

    • they can be big enough to be inserted into ER co-translationally
    • flexibility: one precurosor can generate multiple pepties or different isoforms
  • neuropeptides are evolutionarily older than classical transmitters: used as signaling before neurons exist (ex: yeast mating peptides)

  • can be transported to Golgi for glycosylatio and sulfation, sorted into transport vesicles, and then cleaved from the precursors

    • cleavage can occur in trans-golgi network, like by furin
  • processing

    • signal sequence cleavage in ER
    • endoproteolytic cleavage in TGN (by furin) or secretory vesicle (by PCs)
    • carboxypeptidase (in secretory vesicle)
    • peptidyl-glycine-a-amidation
    • amide is put on
  • sorting into regulated secretory vesicles

    • prehaps by aggregation and drop in pH triggers aggregation of protease and other aggregation-related proteins, but not clear


  • slow transmission via G protein-linked receptor
  • useful anatomical markers to define subsets of neurons
  • used widely by neuroendocine cells in hypothalamus

    • ex: vasopressin and oxytocin
  • neuropeptides are modulatory : often acts as a feedback control

  • play a role in homeostasis, stress, reproduction
  • also modulate behaviour : ex, like whether C-elegans like to eat together or not
  • other specific roles

    • opioids : inhibit pain
    • neuropeptide Y, ghrelin : eating
    • orexin : sleep
    • GRP (gastrin-related peptide) : GRP has to do with formation fo memory to fear
  • use slow synaptic transmission

    • slow transmission, alter the potential fo cells by regulating ion channels, or other properties like cytoskeletal dyanmics

2G-protein coupled receptors


  • 7-transmembrane domains
  • cytosolic terminal : regulates the receptor like turning it off, densentization, internalization

    • also site for G-protein binding and other downstream effects
  • three subunits

    • alpha, beta and gamma (always linked to beta)
    • alpha is the G protein that binds to GTP
    • they're effectors, Gbeta-gamma can be released to do downstream effects

2.2some G protein effectors

  • Adenylate cyclase
    • make cAMP
    • regulate cAMP dependent protein kinase (PKA)
  • phospholipase C
    • make IP and DAG
    • release calcium from internal storage
  • ion channels
    • Ga or G-beta-gamma can binds directly to the channel
    • or second messenger binds to channel cand causes phosphorylation
  • cyclic GMP phosphodiesterase, esp for vision

2.3G protein signaling

  • G protein ligands
    • neurotransmitters: classical and neuropeptides
    • sensory inputs, lipids, cytokines
  • specificity
    • determined by the subtype
      • beta adrenergic receptors bind to Gs and activates adenylate cyclase
      • alpha adrenergic receptors bind to Gi and does the opposite
    • one transmitter can have multiple receptors and oppsite effect on different G proteins
  • histamine:
    • binds H1 receptor -> sleepiness
    • H2 receptor -> allergies

3Slow neurotransmission

  • neuropeptides can change synpatic strength

  • slow EPSP : closing resting K+ channels or opening resting cation channels

  • slow IPSP : resting K+ channels opening are affected
  • shape of action potential : closing of voltage gated K channels or opening of voltage gated Ca channels
  • size of PSP : ligand-gated ion channels and changes in transmitter release
  • can also change resting membrane potential
  • fine-tune neuronal responses