Amino Acids as Neurotransmitters

Question 1

GABA and aspartate are derived from

Answer 1

Glutamate

synthesised in the CNS

Question 2

Glycine is derived from

Answer 2

Glutamate

synthesised in the spinal cord

Question 3

Main NT classes:

Answer 3

1. Amino acids
2. Peptides
3. Monoamines

Question 4

Glial cells outnumber neurons at a ratio of

Answer 4

10:1

Question 5

Neuromodulators:

Answer 5

Cause complex responses/modulation;
Alter sensitivities of synapses;
Modify post synaptic responses;
Change pre-synaptic handling of NT;
Changes occur over minutes, hours or
days;
Associated with slower events,
e.g. growth, learning, protein synthesis

Question 6

Agonistic drug effects:

Answer 6

Drugs bind to autoreceptors and block inhibitory effect

Drugs bind to postsynaptic receptors and either activates them OR increaes the effect on them via neurotransmitters

Drugs block the deactivation of NT molecules by blocking degregation or reuptake

Question 7

Antagonistic drug effects:

Answer 7

Drug activated autoreceptors and inhibits NT release

Drug binds to postsynaptic receptor and blocks the NT

Question 8

BBB

Answer 8

Blood-brain barrier, a system of tight
junctions between the endothelial cells
and surrounding astrocytes of the
capillaries.

Tightly regulated the CNS and prevents toxins entering the brain

May be compromised in diseased states

Question 9

GABA and Glycine are

Answer 9

Inhibitory

Question 10

Glutamate and aspartate are

Answer 10

Excitatory

Question 11

Glutamate can be derived from

Answer 11

Glucose or glutamine

Question 12

Glutamate receptors: Excitatory

Answer 12

NMDA, kainate and AMPA
Ionotropic

Permeable to Na+ and Ca+

Question 13

Glutamate receptors: Inhibitory

Answer 13

Metabotropic receptors (MGluR)

coupled to
phosphatidylinositol metabolism

Question 14

Glycine is an positive allosteric modulator of NMDA receptor glutamate responses. T/F

Answer 14

True

Question 15

Positive allosteric modulators are:

Answer 15

Allosteric ligands that bind to a topographically distinct site
to the orthosteric agonist and enhance the affinity (cooperativity factor-α) and/or efficacy
(modulation factor-β) of the orthosteric agonist.

Question 16

Orthosteric agonists:

Answer 16

bind to the G protein-coupled receptor (GPCR), which induces a
conformational change that results in the activation of downstream signaling, such as
glutamate

Question 17

All ionotropic glutamate receptors are

Answer 17

tetramers

Question 18

When located post-synaptically, these GPCR mGluRs are thought to be largely

Answer 18

excitatory

Question 19

Group II and III receptors predominantly presynaptic, and activation actually
reduces neurotransmission and overall excitability. They can be considered to, in
some cases, function as

Answer 19

autoreceptors

Question 20

It is difficult to selectively block glutamate because:

Answer 20

Glu is so generally used within the CNS

Question 21

Blocking the glycine site on NMDA

receptors effectively is

Answer 21

antagonistic to responsiveness

Question 22

Only two drugs in current
medicinal use, and they are lipid
soluble and can cross the BBB;

Answer 22

– Ketamine (anaesthesia,
analgesia, depression)

– Memantine (Alzheimer’s
Disease)

Question 23

PCP and Ketamine bind to:

Answer 23

The same deep site within the ion
channel of the NMDA receptor, where they block ion
movement into the neuron.

As they bind to an area other than the glutamate
binding site, they are considered to be noncompetitive antagonists of the NMDA receptor.

Question 24

Ketamine binds to:

Answer 24

NMDA and mu opioidreceptors

Question 25

Memantine is also a noncompetitive antagonist on the NMDA receptor. T/F

Answer 25

True

Question 26

Memantine is a clinically useful drug in treating:

Answer 26

moderate to severe confusion (dementia) related to Alzheimer's disease. It may improve memory, awareness, and the ability to perform daily functions

Question 27

very little GABA is found outside of the CNS because:

Answer 27

``` GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD), and only GABAergic neurons have GAD ```

Question 28

GAT1 sit

Answer 28

Presynaptically

Question 29

GAT2/3 sit

Answer 29

Postsynaptically

Question 30

The function of GABA transaminase | (GABA-T):

Answer 30

Recycles GABA so it can be re-used or degradedto glutamine, which can be transported without effect.

Question 31

GABAa receptor motif:

Answer 31

a-b-a-g-a motif. | arranged symmetrically around the central chloride anion conduction pore

Question 32

Benzodiazepines

Answer 32

Positive allosteric modulators, potentiating the effects of GABA, giving the receptors a greater affinity for GABA, increasing the inward Cl- current.

Question 33

Benzos increase inward Cl- T/F

Answer 33

True

Question 34

More GABAa receptors sit

Answer 34

Postsynaptically

Question 35

Activation of GABAa receptors lead to

Answer 35

HYPERpolarisation due to an influx of Cl- ions

Question 36

Activation of GABAa receptors make it LESS likely for an AP to occur due to

Answer 36

the inward movement of Cl- ions,

Question 37

Full GABA agonists within the CNS display

Answer 37

A large number of effects including anti-anxiety (anxiolytic), muscle relaxant, sedation, anti-convulsion, and at high enough doses, anaesthesia.

Question 38

GABAb receptors

Answer 38

are dimers of two different proteins, bound together at the C-termini. B1 and B2 subunits have a GABA binding site linked to 7 transmembrane domain typical of all GPCRs; B2 is coupled to Gi protein.

Question 39

Activation of the heterodimer

Answer 39

inhibits adenylyl cyclase activity via G-proteins

Question 40

Activation of the heterodimer inhibits adenylyl cyclase and

Answer 40

Increases outward K+ Reduces inward Ca2+ conductance; both channel effects reduce post- and presynaptic excitability.

Question 41

Baclofen is a derivative of GABA, | and is an agonist of

Answer 41

GABAb | receptors.

Question 42

Baclofen treats spasicity due to

Answer 42

decreases neurotransmitter release in excitatory spinal pathways, and increases inhibitory pathway activity

Question 43

GHB

Answer 43

is an agonist at GABAA receptors and a partial | agonist at GABAB receptors

Question 44

GHB may induce

Answer 44

nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death.

Question 45

Ionotropic Receptors:

Answer 45

Glycine receptors are pentamers of 5a, 3a:2b or 2a:3b each with a chloride ion channel. There are 4 known a subunits and no metabotropic forms.

Question 46

Synapse clearance:

Answer 46

via transporters with GlyT1 into astrocytes, and GlyT2 into | presynaptic neurons.

Question 47

Strychnine

Answer 47

a toxin obtained from seeds of an evergreen tree, is a competitive antagonist for glycine receptors, binding the blocking access of glycine to its receptors.

Question 48

Tetanus

Answer 48

toxin blocks glycine release from inhibitory interneurons in the spinal cord, resulting in reflex hyperactivity and violent muscle spasms