Neuropeptide Transmitters and their Receptors Flashcards
Dale’s Hypothesis?
A single neurone stoers and releases neurotransmitter(s) from all of its terminals.
What hypothesis did Burnstok devise?
The co-transmitter hypothesis. (NA/5HT) (NA/ATP).
Name 5 neuropeptide families.
1) Substance P and Neurokinins
2) Enkephalins
3) Neuropeptide Y
4) Vasoactive intestinal Polypeptide
5) Calcitonin Gene Related Peptide.
Explain the production of all bioactive peptide.
Synthesised in the cell body, enzymatically cleaved from larger, inactive precursor peptides in the WR, transferred to the Golgi for packing and transported to release sites.
Are levels of neuropeptide expression constant?
No - they can vary depending on stage of development or any pathologies.
Explain NPY production.
Produced from 4 exons in 1 gene. There is regulation at... ...transcription ...translation ...post-transcriptional processing (plus amide group to make NPY active)
CPON (C-terminal peptide of NPY) is also produced, packaged, released and degraded as NPy but is inactive!
Explain Sp and NK production.
Preprotachykinin gene I - SP with or without NKA, NPK, NPY
Preprotachykinin gene II - NKB.
Which receptors do SP, NKA and NKB act on?
SP and NKA - NK1 and 2
NKB - NK3.
How are neuropeptides degraded?
Extracellularly, by peptidases…that hydrolyse numerous unrelated peptides.
eg enkephalinase - degrades anything with a hydrophobic amino acid then tyr/phe.
Inactivates NKA, SP, NKB and NPY.
What does post secretory processing achieve?
Modifies receptor selectivity - NPY is cleaved by DPP4…removes 2 amino acids to make it selective for Y2.
Do all target tissues have the same repertoires of degrading enzymes?
NO - different target tissues have different repertoires of degrading enzymes.
Explain the release of Co-transmitters.
Neuropeptides are stored in large dense core vesicles.
Classic transmitters are stored in small (clear) synaptic vesicles (SSV).
At low frequencies (local Ca++ elevation), SSV exocytosis.
At high frequecies (general Ca++ elevation)- corelease of LDCV and SSVs.
Explainco release of VIP and ACh.
Parasympathetic nerves innervating salivary glands.
Low freq - Ach release on M receptors = sailvary secretion.
High freq - VIP aswell, vascular dilation and increased ACh release.
Explain NPY and NA co release.
In Sympathetic Nerves innervating SM.
Low freq - NA = vasoconstriction
High, INTERMITTENT freq: NPY release.
Low [NPY] = potentiates Na induced vasoconstriction
High [NPY] = Y1 vasoconstriction and inhibiton of NA and NPY release via Y2..
Are all neuropeptides co-released?
NO!
