Intro lecture Flashcards
What are the 5 steps in neurotransmission
- NT synthesis
- Vesicular storage
- Synaptic release
- Binding of NT to receptor
- Termination of action
Where does NT synthesis take place?
Inside the neuron cytosol usually with enzymes present there
Where does termination of action occur?
Can occur at a presynaptic nerve terminal, surrounding glial cells, in the synaptic space, or in the postsynaptic cell.
Describe how drugs can alter NT synthesis
- Enzyme inhibition
- Increased dietary intake of precursors
- Precursor loading
Describe how vesicular storage can be altered by drugs
Inhibition of vesicular transport leaves more NT in the cytosol, where they are subject to enzymatic degradation
Describe how synaptic release can be altered by drugs
Toxins can degrade snares and disrupt fusion of the synaptic vesicles with the cell membrane (e.g., botulinum toxin)
Some drugs also can act presynaptically to increase the amount of drug released
Describe how drugs can alter binding of neurotransmitters to the receptors
Competitive and non-competitive inhibition
Describe how drugs can alter termination of action
Can inhibit or enhance some enzymes to allow shorter/longer action of the NT in the synapse
How is neurotransmitter synthesis different for peptidergic neurotransmission?
Requires not just a precursor molecule and enzyme, but an entire DNA, RNA, and ribosomal unit to transcribe the peptide. It starts as a pre-propeptide, then a propeptide, and then a peptide.
How is vesicular storage different in peptides?
They’re packaged into “dense core vesicles” at the ER and then transported in the same manner
How is synaptic release different in peptides?
They’re stored farther away from the synaptic terminal, so it takes a larger stimulus to achieve release.
How is peptide receptor action different?
They travel farther, and the interaction is much more complex and not very well-understood. They cannot cross the BBB.
How is termination of peptides different?
They are not taken up into the nerve terminal; they’re usually just cleaved by peptidases.
Metyrosine binds to what?
Tyrosine hydroxylase
What is the consequence of metyrosine physiologically?
Decreases production of dopamine (lowers blood pressure by reducing NE production)
