Principles of Neurotransmission Flashcards
What is a classical neurotransmitter?
it is synthesised in synaptic terminal. Enzymes are synthesised at RER and there is axonal transport of enzymes to terminal.
What is an atypical neurotransmitter?
Peptide structure - proteins are synthesised in the NUCLEUS, normally precursors that are cleaved by proteolytic enzymes to make the peptide hormone EG POMC (proopriomelanocortin) - cleaved into ACTH, MSH, CLIP etc
List the 3 neurotransmitter classes
Classical - synthesised at terminal
Atypical - peptide
Gases - Nitric oxide
What is Sildenafil? How does it work?
Viagra! acts by inhibiting PDES, the enzyme that breaks down cAMP (the effector molecule of NO). NO stimulates GC –> cAMP –> NO –> vasodilation –> erection.
Sildenafil stops the reduction of cAMP.
2 ways Ca++ increased in synaptic knob
- Calcium channels
2. ER release - phospholipase C –> PIP –> Ca++ release from ER
What causes the docking of the synaptic vesicle with membrane
Called SNARE proteins - they mediate vessicle fusion:
Presynaptic:
Synaptobrevin, Synaptotagmin
Postsynaptic:
Syntaxin, SNAP-25
How does botulism and tetanus act on neurotransmitter release - answer on molecular level
Botulism cleaves SNARE proteins, Ach cannot be released. Used also as botox
Tetanus toxin travels up the axon, reaches spinal cord where the neuron originals from, and acts on the GABA INHIBITORY neurons (blocking Gaba release) thus BLOCKING INHIBITION of motor neurons = contraction.
Name 3 ways in which a neurotransmitter is removed from a cleft
Reuptake
Diffusion - peptides will diffuse
Enzymatic degradation
Discuss action time of classical vs atypical
Classical- v. short time to act
Atypical - peptides longer time, can diffuse further.
What is the most efficient way to interrupt signal of classical neurotransmitters?
Reuptake
Discuss the location of the receptors for neurotransmitters
For axo-axonic - there are 2 kinds:
- post synaptic
- presynaptic (auto and heteroreceptors)
Discuss autoreceptors
Regulate the synthesis and release of neurotransmitters. Only one neurotransmitter (Noradrenaline) can act on both post synaptic receptors and presynaptic (alpha2) receptors for adrenaline. Can act as negative feedback inhibiting further release of NE.
What mechanism can you use to increase the function of a neurotransmitter? [6]
- increase synthesis
- decrease storage in vessicles
- increase release
- block reuptake
- inhibit degradation enzyme
- use agonist for receptor
How do you affect neurotransmitter storage?
Reserpine - a drug that blocks VMAT (which normally carries NE into the vessicle)
What is reserpine? Why can’t it be used as antihypertension?
A drug that blocks VMAT and stops neurotransmitter storage into vessicles. If you block storage of neurotransmitter in brain = depression
What drug do you use for Parkinsons
Levadopa- precursor to dopamine
What is Fluoxitine?
Selective serotonin reuptake inhibitor (like Fluvoxamine),which increases serotonin function and has antidepressant action.
What does Cocaine do?
Blocks reuptake of noradrenaline in the periphery and dopamine in the brain = stimulation.
What does amphetamines do
Blocks reuptake of dopamine and noradrenaline, also blocks Monoaminoxidase (responsible for degrading dopamine, serotonin and noradrenaline)
When would we use an AchE INHIBITOR therapeutically
Alzheimers because Ach is important for cognitive function.
What is cotransmission - give examples of each in terms of parasympathetic and sympathetic.
release of more than one neurotransmitter at the same time from same terminal:
Parasympathetic: Ach classic, NO classical /VIP (vasoactive intestinal peptide = vasodilator)
Sympathetic: ATP (classical), NA (classical), NPY = neuropeptide Y = increases motivation to eat.
Explain SSV and LDV
Small light vessicles (clear vessicles) contain classical neurotransmitter. They have low affinity, so need to be close to the calcium channel.
Large dense core vesicles = peptide.
For classical you need one low frequency stimulation, but for peptide you need high frequency.
SSV is close to presynaptic, activated by voltage gated Ca++ channels
LDCV are more distant and have higher affinity. At dendrites you also have ER Ca++ release.
Discuss the three mechanisms of cotransmission / neuromodulation
- potentiation / cooperation
- inhibit each other / antagonise
- point to point / vs distant
Which 2 peptides are released from dendrites?
- oxytocin - affecting brain function if released from dendrites.
- vasopressin (ADH)
Both produced in hypothalamic neurons and normally secreted in posterior pituitary.
What is the effect of administration of alpha-MSH
dendritic release of oxytocin, reducing secretion from posterior pituitary, inhibiting firing rate.
Functions of oxytocin
Lactation, uterine contractions, but also bonding behaviour, affiliative social behaviours etc.
What is neurotransmitter switching?
One kind of neuron can switch the type of neurotransmitter that is makes according to changes in environment. Eg: Hypothalamus is concerned with interaction with environment. Neuron can switch from dopamine to somatostatin (GHIH) production depending on condition. Eg mouse in the dark example.
