Presynaptic Nt transmission Flashcards
3 types of NT
- amino acids
- amines
- peptides
steps to protein
amino acid - peptide - poly peptide - protein
criteria for classifying NTs
- synthesis and localization
- release
- response mimicry
- inactivation
Synthesis
the candidate NT and its enzyme must be shown to be contained in the same neuron or axon terminal
methods of synthesis/localization
- immunocytochemistry
- in situ hybridization
immunocytochemistry
Using labelled antibodies to anatomically localize NTs or enzymes that make it
steps of immunocytochemistry
- Nt candidate is injected into animal
- antibody should attach to candidate
- antibody is taken out and dyed
- inject it back into the cells and it so they will color the cells that cntaint that NT
In situ hybridization
- tagging a strand of complementary mRNA which synthesizes a molecule
steps of in situ hybridization
- build synthetically a a complementary mRNA strand to the one of interest
- color that mRNA
- see if where it attaches to the mRNA that synthesizes the enzyme of interest
release
NTs released by the presynaptic neuron must be released once activated
How to show release
- taking a smaple of fluid that bathes the neurons and testing whether it mimics the activity of the intact synapses
optogenetics
using light to stimulate one specific type of Nt in the brain at a time
response mimicry
in experiments, the candidate must produce a response that is the same of the response of the post synaptic neuron to that NT
methods for release
optogentics
Iontophresis
- Nt candidate is dissolved in a solution that gives it a net charge. then is slowly released from a pipette next to the presynaptic membrane of a neuron to see if iy has the same effects as the NT
Inactivation
- molecule needs to be actively removed from synaptic cleft
- degradation or reuptake
Peptide synthesis
peptides are synthesized in the soma of the neuron and transported by the secretory granules to the axon terminal
synthesis of amines and amino acids
they are synthesized from precursor molecules in the cytosol and stored in vesicles in the axon terminal
- precursors are modifified by by enzymes
dale’s principle
one Nt is made in one cell
- false, there could be different NTs in one cell
Rate limiting steps
-a controllling step allows for the overall control of Nt synthesis
- to regulate
Amine NT
- acetylcholine
- catecholamines
- serotonin
synthesis of acetycholine
- the enzyme ChAt is made in the soma and then syntheiszes ACh in the terminal from choline (precursor) and acetyl
- then degraded back into acetic acid and choline by AChe
catecholines
- dopamine
- norepinephrine
- epinephrine
precursor of catecholimes
Tyrosine
steps of catecholamines
- hydroxylation: tyrosine –> dopa
- decarboxylation: dopa –> DA
norepinephrine
precursor is dopamine
epinephrine
precurosr norepinephrine
Degradation of catecholmines
- MAO
- COMT
Steps of serotonin synthesis
- hydroxylation (adding HO)
- decarboxylation (take away
precursor of serotonin
trytophan
degradation of srotonin
degraded by MAO
Amino Acids neurotransmitters
- glutamate
- glycine
- GABA
glutamate
- main excitatory NT in the brain
glycine
- inhibitory NT is found primarily in spinal cord, brainstem and retina
GABA
- most common inhibitory Nt in the brain
- epilepsy
precursor to GABA
glutamate is the precursor to GABA
- uses GAD (glutamic acid decarboxylase)
neuropeptides
- substance P
- opiod peptides (endorphines)
- morphine and heroin are exogenous opioids and bind to opiod receptors
- pain perception
retrograde messenger
- endocannabinoids and nitric oxide are retrograde
Agonists
- facillate postsynaptic effects
- mimics effects of neurotransmitters
antagonist
- drugs that prevent normal functioning of NT
How drugs enhance transmission
- as precurosrs for synthesis
- activatin receptors directly
- block degrading enzymes
- block reuptake
- increase NT release
how drugs inhibit transmission
- reducing synthesis
- make vesicle leak
- block receptors
inhibite depolarization
Ach synthesizing enzyme
choline acetyltransferas (ChAT)
degrading of ACh
- broken by Aceylcholineterase (AChE)
- broken into acetic acid and choline
rate limiting step of ACh
bringing choline back in
what does L-dopa treat and how
its used to treat parkinsons by increases DA available for release
- l-dopa increases synthesis
enzyme in hydroxylation of cathecolamines
tyrosine hydroxylase synthesizes tyrosine to dopa
TH is the rate limiting step
enzyme for dopa to da
dopa decarboxylase
how do antipsychotics work
they block DA receptors and autoreceptors
- DA antagonist
how does cocaine work
blocks reuptake of dopamine
enzyme for DA to NE
Dopamine-B-hydroxylase
enzyme for NE to EPI
PNMT
- degraded by MAO and COMT
Prozac
- aka fluoxetine
- blocks reuptake of serotonin which increases its levels
-ssri
antidepressant iproniazid
- blocks MAO inhibitors for serotonin
excitotoxicity
when glutamate is in excessive quantities
- can cause strokes
Apomorphine acting of DA receptors
it activates the receptor directly
amphetamine
increases DA release
AMPT
reduces synthesis of DA by inhibits the enzyme TH
