Lecture 9: Neuropeptides And Hormones Flashcards
What are peptide neurotransmitter’s composition?
Small proteins, made up of the 20 amino acids; joined by peptide bonds
Neuropeptide
Peptides that serve as neurotransmitters; can also serve as hormones
Neuropeptide synthesis 4 steps
- Neuropeptide are encoded by genes; “prepropeptides”; regulated like any other protein in the body
- Prepropepide mRNA trans locates to the ER, guided by a “signal peptide”
- Signal peptidase cleaves bond between the prepropeptide and signal peptide —> propeptide
- Propeptide is released from the ribosome that undergoes extensive posttranslational modification to become the active neuropeptide (cleavages and modifications at specific amino acid residues)
What are the 6 steps involved in the processing of POMC?
- The POMC gene encodes the propeptide for a number of active neuropeptides including ACTH, beta-endorphins, and melanocyte-stimulating hormone or MSH (Prepropeptide)
- The prepropeptide is translocated to the ER where it is translated into propeptide
- The propeptides are processed by prohormone convertases 1 and 2 (PC1 and PC2); stepwise reaction, cleaving certain dibasic residues (eg: Lys-Arg; Lys-Lys; Arg-Arg and Arg-Lys) —> smaller peptides with Lys and Arg at their N and C termini
- Carboxypeptidase E (CPE) and aminopeptidase remove these basic residues
- N terminal acetylation via N-acetylransferases can occur which regulates the activity of the neuropeptide (effect of acetylaton depends upon the particular peptide being processed)
- Amidation of glycine on C-terminus can occur via PAM
When is alpha-MSH activity increased?
Increased by N-terminal acetylation of POMC
What does N-terminal acetylation of POMC do?
Beta-endorphin activity is decreased
And alpha-MSH activity is increased
The specific neuropeptides synthesized from a prepropeptide gene depend on what? (POMC)
Upon the tissue because different tissues contain different prohormone convertases
For many prepropeptide genes, what does alternative mRNA splicing?
Can yield multiple gene products
What are are neuropeptides synthesized by?
Transcription, translation and posttranslational modifications in the cell body and axon (similar to any other protein)
Where are neuropeptides stored?
In large, dense core vesicles that are assembled in the Golgi network
How are the dense core vesicles containing neuropeptides transported?
Down the axon on microtubules
Where are dense core vesicles containing neuropeptides docked?
Outside of the active zone and are released upon large and sustained calcium entry into the cell (rapid train of action potentials)
Many neuropeptides are _____ with small ______ molecules
Co-localized
Neurotransmitter
What happens to neuropeptides under low stimulation conditions?
The small neurotransmitter vesicles will be mobilized and fuse with the membrane
What happens to neuropeptides under high stimulation conditions?
The dense core vesicles will be mobilized and fuse with the membrane
Within the striatum, what do D1 dopamine receptors do?
D1 dopamine receptor expressing striatonigral GABAergic neurons colocalize GABA with both Substance P and Dynorphin
Within the striatum, what do D2 dopamine receptors do?
D2 dopamine receptor expressing striatopallidal GABAergic neurons colocalize GABA with enkephalins
What are the receptor types for neuropeptides?
The vast majority of cases, they are G protein coupled
How do you get far reaching effects?
Disconnecting the receptor and neuropeptide localization in brain
Neuropeptides bind with _____ affinity
Very high affinity (nM range vs small neurotransmitters which bind in muM range)
What accounts for neuropeptides ability to interact with receptors?
The fact that they are flexible molecules
Can neuropeptides cross the BBB?
NO! And therefore they are not suitable for treating brain dysfunction
Opiates
Compounds purified from crude opium (opium poppies); specifically morphine, codeine and papaverine
Opioids
Include any molecule exhibiting the properties of opiates, including synthetically produced molecules such as heroin (which is produced by altering the structure of morphine)
