ST 4.4 Peptides and Gases

What are the 3 ways in which peptide transmitters are different from classical transmitters?

They are formed in the cell body, they are not re-uptaken, and they are packaged in dense core vesicles.

Where specifically are peptide NT synthesized?

ribosomes in the cell body.

What are prepropetides?

They are initially made as large precursors with a "pre" signal sequence that directs them through the ER to the golgi.

Where are peptide NT packaged?

In the golgi.

What is post translational modification?

As vesicles travel down the axon, enzymes cleave the pre-propeptide into the final NT.

What are the advantages of post translational modification?

Diversity and folding.

Explain diversity in post translational modification.

A single precursor can yield different final peptides depending on the specific enzymes present in the cell.

Explain folding in post translational modification.

Large precursors are often necessary to allow the peptide to fold correctly.

What is mRNA splicing?

mRNA is cut differently before translation (also leads to diversity).

When are dense core vesicles generally released?

during high frequency action potential bursts.

What calcium level is needed to release dense core vesicles?

low levels.

How are peptide NT reuptaken.

They are not.

How are peptide NT terminated?

either by diffusion or degradation by extracellular peptidases.

What was the goal of the vesicle processing experiment.

To determine if peptide cleavage occurs during transport.

What was the method of the vesicle processing experiment.

Use long axon systems and sample vesicle contents at different distances.

What was the finding of the vesicle processing experiment.

Proximal areas contain mostly intact precursors. Distal regions contain final peptide. Therefore, cleavage occurs down the axon.

What was the goal of the peptide diffusion experiment?

To see how far a peptide travels after release, since it does not get reuptaken.

What was the method of the peptide diffusion experiment?

In the dorsal horn of the SC, researchers used a glass pipette with antibodies to bind normal Neurokinin A and then replaced the empty spaces with radioactive Neurokinin A.

What was the finding of the peptide diffusion experiment?

The peptide travelled deep into the tissue, confirming that without reuptake, peptides act over a much larger area than a classic NT.

NO synthesis pathway

Arginine --(NOS + cofactors)--> NO + Citrulin

How is NOS activated

Ca2+ influx.

How is NOS regulated?

Phosphorylation

How is NOS inhibited?

By PKC.

How is NO released?

It diffuses across the membrane; it has no vesicle.

What is the action of NO?

Activates guanylyl cyclase to produce cGMP or perform s-nitrosylation of proteins.

What is s-nitrosylation?

Altering the structure of proteins.

How is NO action terminated?

automatically terminated when the gas bumps into a protein and reacts.

CO synthesis pathway

Heme --(heme oxygenase)--> biliverdin, CO, and Fe

How is CO synthesis activated?

By phosphorylation via PKC.

What is the action of CO?

It activates guanylyl cyclase to generate cGMP.

What is the synthesis pathway of H2S.

L-Cysteine --(CSE/CBS)--> L-Serine + H2S

What is the action of H2S

It causes vasodilation and activates K-ATP channels leading to hyperopolarization.

Argument 1 for NO as a NT?

It has a unique synthetic pathway. NOS is not found everywhere and is uniquely activates by Ca2+ and calmodulin.

Argument 2 for NO as a NT?

Its synthesis and release via diffusion are triggered by neuronal activity, specifically calcium influx through NMDA receptors.

Argument 3 for NO as a NT?

It has clear action such as activating guanylyl cyclase to produce cGMP or performing S-nitrosylation.

Argument 4 for NO as a NT?

It acts as a retrograde messenger allowing the post synaptic cell to communicate back to the presynaptic terminal.

Argument 1 for NO NOT being a NT?

NO is not stored in vesicles; it is immediately diffused.

Argument 2 for NO NOT being a NT?

It does not undergo regulated exocytosis at a synapse. It instead diffuses in all directions.

Argument 3 for NO NOT being a NT?

It does not bind to membrane-bound receptors. Instead, it enters the target cell directly to interact with intracellular enzymes or proteins.

Argument 4 for NO NOT being a NT?

There is no reuptake or specific enzymatic degradation mechanism. Its action simply terminates when it reacts with a protein.