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Flashcards in Lecture 4 Chemicals in the Brain Deck (59)
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1

what are the types of neurotransmitters

amino acids
monoamines
acetylcholine - fast
neuropeptides - slow

2

how are neurotransmitters stored and released

Synthesized locally in presynaptic terminal
Stored in synaptic vesicles
Released in response to local increase in Ca2

3

how are neuropeptides stored and released

Synthesized in the cell soma and transported to terminal
Stored in secretory granules
Released in response to global increase in Ca2+

4

how are fast neurotransmitters released

close to voltage gated ca2+ channels in terminal so released in short bursts when membrane depolarised

5

how are slow neurotransmitters released

stored in vesicles further from membrane so release slower as must migrate so released when ca2+ released sufficiently

6

what are amino acid transmitters

glutamate
GABA
Glycine

7

what are excitatory neurotransmitters

slightly depolarises the post synaptic cell's membrane
glutamate (cns)

8

what are inhibitory neurotransmitters

slightly hyper polarises the post synaptic cell's membranes
GABA (brain)
Glycine (spinal cord and brainstem)

9

what do diffuse modulatory systems do

Serotonin
Nt synthesised in small set of neurons, usually in brainstem and then acts across a large area
1 synthesising neuron can affect >100,000 neurons

10

what is the function of diffuse modulatory systems

mood
sleep
pain
emotion
appetite

11

why have multiple neurotransmitters

release of neurotransmitters (other than GABA or Glu) tends to activate or inhibit entire circuits of neurons that are involved in particular brain functions

12

how is glutamate made

synthesised in presynaptic terminal from 2 sources:
1) from glucose via the Krebs cycle
2) from glutamine converted by glutaminase into Glutamate

13

how is glutamate stored

loaded and stored in vesicles by vesicular glutamate transporters (VGLUTs)

14

how is glutamate recycled

reuptake by excitatory amino acid transporters (EAATs) in the plasma membrane of presynaptic cell and surrounding glia (convert Glu to glutamine and this is transported from the glia back to nerve terminals where it is converted back into Glu)

15

how is GABA made

synthesised from glu in a reaction catalysed by GAD

16

how is GABA stored

loaded and stored into vesicles by a
vesicular GABA transporter, GAT
(Gly uses the same transporter)

17

how is GABA recycled

cleared from synapse by reuptake using transporters on glia and neurons including non-GABAergic neurons
higher proportion of GABA is made de novo to refill vesicles rather than recycling to ensure enough as can be kept at Glu

18

what happens with too much Glu/too little GABA

hyper-excitability
epilepsy and excitotoxicity
eg cerebral ischaemia (electrochemical gradient abolished, Na+/K+ reversed, transporters release Glu in reverse, excitotoxic death (ca2+, enzymes, digestion)

19

what happens with too much GABA

sedation/coma
eg GHB (date rape drug), GABA metabolite converted back to GABA

20

what are the types of monoamines

catecholamines and indolamines

21

examples of catecholamines

Dopamine
Epinephrine (adrenaline)
Norepinephrine

22

examples of indolamines

serotonin

23

how does dopamine synthesis occur

step 1 of catecholamine synthesis
tyrosine (TH) to dopa (Dopa DC) to dopamine (DA)

24

how can Parkinson's be treated with dopamine

administration of
Levodopa (L-DOPA)
Dopa DC converts it to DA to inc amount

25

how is dopamine turned to epinephrine

catecholamine synthesis 2
DA (DBH) to NE (PNMT) to E
DBH located in synaptic vesicles only, and NE is the only transmitter synthesised within
vesicles

26

how are catecholamines stored

Loaded into vesicles by vesicular monoamine transporters (VMATs)
(proton gradient like Glu and GABA transporters)

26

how are catecholamines stored

Loaded into vesicles by vesicular monoamine transporters (VMATs)
(proton gradient like Glu and GABA transporters)

26

how are catecholamines stored

Loaded into vesicles by vesicular monoamine transporters (VMATs)
(proton gradient like Glu and GABA transporters)

27

how are catecholamines released

released by Ca2+ - dependant exocytosis
binds and activates receptor

28

how are catecholamines recycled

signal terminated by reuptake into the presynaptic axon terminal by transporters powered by electrochemical gradient (Dopamine transporters (DATs), Norepinephrine transporters (NETs))

29

what happens to catecholamines once back in cytoplasm

reloaded back into vesicles
enzymatically degraded by Monoamine oxidases (MAOs) or inactivated by Catechol-O-methyl-transferase (COMT)

30

how do amphetamines modulate catecholamine release and reuptake

reverses transporter, so pumps out transmitter and blocks reuptake (DA & NE)

31

how does cocaine and methylphenidate modulate catecholamine release and reuptake

(eg Ritalin) block DA reuptake into terminals
More DA in synaptic cleft – extended action on postsynaptic neuron

32

how does selegiline modulate catecholamine release and reuptake

MAO inhibitor (in dopaminergic nerve terminals)
stop breakdown of DA, more released on subsequent activations (treatment of early-stage PD, depression and dementia), and overall increasing the available amount of DA

33

how does entacapone modulate catecholamine release and reuptake

COMT inhibitor (treatment of PD), increases the available amount of neurotransmitter

34

how is serotonin synthesised

tryptophan to 5-HTP to Serotonin aka 5-HT

35

how is serotonin stored

vesicles

36

how is serotonin recycled

signal terminated by reuptake (Serotonin transporters (SERTs)) on presynaptic membrane
destroyed by MAOs in the cytoplasm

37

how does fluoxetine affect serotonin release and reuptake

(eg Prozac) blocks reuptake of serotonin (SSRI – selective serotonin reuptake inhibitor) (treatment of depression, OCD)

38

how does fenfluramine affect serotonin release and reuptake

stimulates the release of serotonin and inhibits its reuptake (has been used as an appetite suppressant in the treatment of obesity)

39

how does MDMA affect serotonin release and reuptake

causes NE and serotonin transporters to run backwards, releasing neurotransmitter into synapse/extracellular space (therapeutic potential in PTSD?)

40

how is Ach made

Choline acetyltransferase (ChAT, CAT)
converts choline+Acetyl CoA (coenzyme A)
into acetylcholine

41

how is Ach stored

packaged into vesicles by vesicular acetylcholine transporter (VAChT).

42

how is Ach broken down

rapidly degraded in synaptic cleft
by acetylcholinesterase (AChE)
Choline is transported back into the
presynaptic terminal and converted to
acetylcholine

43

how does AchE modulate Ach degradation

block the breakdown of ACh, prolonging its actions in the synaptic cleft
e.g. Neostigmine (treatment of myasthenia gravis, MG)

44

how are neuropeptides different from small molecule transmitters

Vary in their methods of synthesis and
release from small molecule transmitters

45

what are neuropeptides

Short polypeptide chains (3 to 36 amino acids)
Over one hundred neuropeptides described
e.g. endorphins, neuropeptide Y, substance P, endogenous opioids, vasopressin

46

how are small molecules transmitted

synthesised in cell body
slow axonal enzyme transport
synthesis and packaging of nt
released, diffusion
transport of precursors into terminal

46

how are small molecules transmitted

synthesised in cell body
slow axonal enzyme transport
synthesis and packaging of nt
released, diffusion
transport of precursors into terminal

47

how are peptides transmitted

synthesis of nt precursors and enzymes in cell body
transport down microtubule tracks
enzymes modify precursors to produce them
diffuse
degraded by proteolytic enzymes

48

how does neuropeptide degradation vary from small molecules

neuropeptide vesicle membrane recycled but not refilled

bind to and activate receptor

neuropeptides signalling is terminated by diffusion from site of release and degradation by proteases in the extracellular environment

49

how does neuropeptide release vary from small molecules

needs sustained or repeated depolarisation of Ca2+
release is slower than small molecule release and signals may be maintained for longer

50

what are other transmitters (retrograde signalling)

soluble gases - NO and CO
Endocannabinoids

51

how is NO made

NO made in postsynaptic neuron by NO synthase (activated by the binding of Ca2+ and calmodulin)

51

how is NO stored

not stored but rapidly diffuses from its site of synthesis. Diffuses between cells (into presynaptic cell - retrograde transmitter)

52

what does NO do

Activates guanylyl cyclase which makes the second messenger cGMP

53

how is NO eliminated

in a few secs of being produced NO is converted to biologically inactive compound

54

what is NO used for

Potentially useful for coordinating activities of multiple cells in a small region (tens of micrometers)

55

what are Endocannabinoids

Small lipids which mostly cause reduced GABA release at certain inhibitory terminals (lower inhibition)
cannabinoid active component in marijuana