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brain form and function > Topic 4 (neurotransmitters and receptors) > Flashcards

Topic 4 (neurotransmitters and receptors) Flashcards

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1
Q

what are 6 types of receptors?

A 
photoreceptor (light)
mechanoreceptor (touch)
t cell receptor (immunology)
complement receptor (immunology)
binding site receptor (pharmacology)
drug/toxin target receptor (pharmacology)
neurotransmitter/neurohormone receptor
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2
Q

what are 3 possible locations for receptors with examples

A

PLASMA MEMBRANE RECEPTORS
ligand gated ion channels
g-protein coupled receptors
intrinsic enzyme receptors

INTRACELLULAR RECEPTORS
e.g ryanodine receptors

NUCLEAR (nucleus) RECEPTORS
interact with DNA e.g steroid receptors

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3
Q

how many subunits are in nicotinic receptors?

A

5 subunits, each which 4 transmembrane domains

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4
Q

what are 4 examples of nicotinic receptors?

A

Nicotinic acetylcholine receptors
GABAa receptors
5HT3 (Serotonin) receptors
Glycine receptors

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5
Q

how many subunits are in ionotropic glutamate receptors?

A

4, each with 3 transmembrane domains

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6
Q

how do ligands bind to ionotropic glutamate receptors?

A

the ligand binding domain acts like a clamshell when the ligand binds

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7
Q

what are 3 examples of ionotropic glutamate receptors?

A

NMDA receptor
AMPA receptor
Kainate receptor

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8
Q

name 5 excitatory ligand gated ion channels

A 
acetylcholine receptor
serotonin receptor
NMDA receptor
AMPA receptor
Kainate receptor
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9
Q

name 2 inhibitory ligand gated ion channels

A

GABAa, Glycine

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10
Q

how many transmembrane domains are g protein coupled receptors made of?

A

7

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11
Q

where does the neurotransmitter bind to in rhodopsin like g-protein coupled receptors

A

the ligand binds to the transmembrane domains, either extracellularly or within the membrane

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12
Q

what are 6 examples of rhodopsin like G protein coupled receptors?

A 
muscarinic acetylcholine receptors
noroadrenergic receptors
opioid receptors
serotonergic receptors (except 5ht3) 
neuropeptide y receptors
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13
Q

where does the ligand bind in metabotropic glutamate receptors?

A

theres a large n terminus where the ligand binds like a venus fly trap

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14
Q

what are 2 examples of metabotropic glutamate receptor like receptors?

A

GABAb

Metabotropic glutamate receptors

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15
Q

what GABA receptors are ionotropic or metabotropic

A

GABAa and GABAc are ionotropic

GABAb is metabotropic

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16
Q

How does the g protein coupled receptor activate the g protein?

A
  1. GDP is bound to the alpha subunit of the G protein
  2. Receptor activation causes GDP to be exchanged for GTP causing the alpha subunit (with the gtp) to dissociate from the B,Y subunit
  3. The alpha subunit and GDP then activates intracellular pathways. For example it binds to adenyl cyclase. Adenyl cyclase then converts ATP to cAMP which activates PKA to phosphorylate Calcium channels causing an influx of calcium ions
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17
Q

name 3 types of neurotransmitters with examples?

A

MONOAMINES

  • dopamine
  • noradrenaline
  • serotonin

AMINO ACIDS

  • Glutamate
  • GABA
  • Glycine

NEUROPEPTIDES

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18
Q

Name 5 ligand gated ion channel neurotransmitters

A

EXCITATORY

  • serotonin
  • glutamate
  • acetylcholine

INHIBITORY

  • GABA
  • Glycine
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19
Q

Name 7 examples of G protein coupled receptor neurotransmitters

A
  • dopamine
  • noradrenaline
  • serotonin
  • Glutamate
  • GABA
  • Acetylcholine
  • -Neuropeptides
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20
Q

Name 4 examples of neurotransmitters with both ligand gated ion channels and g protein coupled receptors

A
  • serotonin
  • glutamate
  • gaba
  • acetylcholine
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21
Q

Name 3 neurotransmitters that are G protein coupled receptors only

A

dopamine
noradrenaline
neuropeptides

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22
Q

name one neurotransmitter which only has ligand gated ion channels

A

Glycine

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23
Q

Descripe DOPAMINE

A
  • it is a monoamine
  • it is a precursor for noradrenaline
  • it acts as a modulator via g protein coupled receptors
  • D1 receptors are excitatory, D2 receptors are inhibitory
  • its involved in movement control, emotion, reward ad addiction
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24
Q

Describe NORADRENALINE

A
  • it has modulatory actions via g protein coupled receptors
  • a1 and b receptors are excitatory
  • a2 receptors are inhibitory
  • its involved in arousal, blood pressure regulation, mood control
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25
Q

Describe SEROTONIN (5HT)

A
  • it has modulatory actions via G protein coupled receptors (except 5HT3)
  • its involved in sleep, appetite, thermoregulation, pain, depression, anxiety, OCD, schizophrenia
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26
Q

Outline the monoamine transmission pathway

A
  1. synthesised in the neuron
  2. stored in vesicles via active transport (vescicular monoamine transporter)
  3. released from the nerve terminals via excocytosis
  4. Acts on target receptor
  5. Removed from the synaptic cleft via monoamine transporter into glial cells or presynaptic neuron
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27
Q

outline monoamine oxidase

A
  • they can be metabolised by monoamine oxidase (MAO)
  • monoamine oxidase is located on the mitochondrial membrane
  • monoamine oxide metabolises dopamine, noradrenaline and seratonin
  • Dopamine is metabolised by MAOa and MAOb
  • Noradrenaline and serotonin are metabolised by MAOa
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28
Q

Outline COMT (Catechol-o-methyl transferase)

A
  • it metabolises monoamines
  • its located in post synaptic neurons and glia
  • it has soluble or membrane bound forms
  • it metabolises dopamine or noradrenaline
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29
Q

what are 4 dopaminergic pathway’s

A

Nigrostriatal pathway

Mesolimbic pathway

Mesocortical pathway

Tuberoinfundibular pathway

30
Q

what is the pathway, role and pathology of the nigrostriatal pathway

A
  • from the substantia nigra to the striatum
  • role is in movement
  • degenerates in parkinsons disease
31
Q

What is the pathway, role and pathology of the mesolimbic pathway

A
  • goes from the Ventral Tegmental area to the NA, hippocampus and amygdala
  • it is involved in motivation and reward
  • it is implicated in addiction and drug dependence
32
Q

what is the pathway role and pathology of the mesocortical pathway

A
  • it goes from the ventral tegmental area to the cortex
  • its involved in cognition, motivation and emotion
  • it is implicated in schizophrenia
33
Q

What is the pathway and role of the tuberoinfundibular pathway

A
  • it goes from the hypothalamus to the medium eminence

- its involved in prolactin release from the pituitary gland

34
Q

How is dopamine syntheised

A
  • tyrosine is converted to L-dopa by tyrosine hydroxylase

- Ldopa then gets converted to dopamine by aromatic l-amino acid decarboxylase

35
Q

how is dopamine stored?

A

its stored in vescicles by vesicular monoamine transporter

36
Q

how is dopamine released?

A

its released by calcium dependent vesicular release

mostly at the end terminal

sometimes at en passant varicosities, meaning places along the axon where neurotransmitters can be released

37
Q

what dopamine receptors are there

A
  • all dopamine receptors are g protein coupled receptors
  • D1like receptors include D1 and D5 and are coupled to stimulatory Gs proteins

D2like receptors include D2, D3 and D4 and are coupled to inhibitory Go or Gi proteins

38
Q

describe dopamine reuptake

A

dopamine is taken up into the axon terminal by the dopamine active transporter (DAT)
this cotransports dopamine with chloride and sodium ions

39
Q

What can dopamine get degraded into?

A

Aldehyde Dehydrogenase or 2-methoxydopamine

Either of these can then be further degraded to homovaillic acid

40
Q

what are the three enzymes involved in degrading dopamine

A

monoamine oxidase
catechyl-o-methyltransferase
aldehyde dehydrogenase

41
Q

outline how drugs afftect the dopamine system

dont need to memorise all drugs

A

DRUGS AFFECTING SYNTHESIS
levo dopa

DRUGS AFFECTING STORAGE
reserpine
methamphetimine

DRUGS AFFECTING RELEASE
amantadine

DRUGS AFFECTING RECEPTORS
full agonists: DA, apomorphine, bromocriptine
antagonists: haloperidol, chloropromazine

DRUGS AFFECTING REUPTAKE
cocaine, buproprion, methylpenidate (ritalin)

DRUGS AFFECTING DEGRADATION
MAO inhibitors
COMT inhibitors

42
Q

outline the synthesis of noradrenaline

A

synthesised from dopamine

by dopamine-b-hydroxylase (found only in noradrenic neurons)

43
Q

how is noradrenaline stored

A
  • dopamine is taken up into vesicles by vesicular monoamine transporter 1 and 2
  • within the vesicles dopamine is converted into noradrenaline
  • a proton pump keeps the intracellular proton concentration high to make sure there is always a gradient for the ATP dopamine transporters
44
Q

what are the two noradrenergic pathways?

A

locus coeruleus nuclei

caudal raphe nuclei

45
Q

where does the noradrenergic locus correleus nuclei project to?

A

frontal cortex, thalamus, hypothalamus, limbic system, cerebellum

46
Q

where do noradrenergic neurons from the caudal raphe nuclei project to?

A

ascend to the amygdala

Descend to the spinal chord

47
Q

how are noradrenergic pathways linked to pathology?

A

low NA transmission is linked with depression

noradrenergic pathways can affect blood pressure

48
Q

how is serotonin synthesised

A

from tryptophan to 5hydroxytryptophan to serotonin

using the enzymes tryptophan hydroxylase and aromatic L-amino acid decarboxylase

49
Q

Describe the serotonergic rostral and caudal raphe nuclei pathways

A
  • involved in sleep, mood appetite and sensory transmission
  • rostral raphe nuclei ascend to cerebral cortex, limbic regions and basal ganglia
  • caudual nuclei descend to medulla and spinal chord
50
Q

how is serotonin implicated in pathology

A
  • low serotonin involved in depression

- different receptors involved in migraine, anxiety, emesis and psychosis

51
Q

describe glutamate

A
  • glutamate is an amino acid neurotransmitter
  • its ionotropic receptors are NMDA, AMPA and Kainate and they are excitatory
  • its metabotropic receptor is mGluR and it is inhibatory
52
Q

Describe GABA

A
  • gaba is the major inhibitatory neurotransmitter
  • its ionotropic receptor is GABAa
  • its metabotropic receptor is GABAb
53
Q

describe glycine

A
  • inhibitory ionotropic receptors
54
Q

how is glutamate synthesised?

A
  • synthesised in the brain from the metabolism of glucose in neurons and glutamine in astrocytes
55
Q

how is glutamate stored?

A
  • it is stored in synaptic vescicles

- these vescicles actively accumulate glutamate via the vesicular glutamate transporter

56
Q

describe the reuptake of glutamate

A
  • glutamate is taken up by excitatory amino acid transporters on presynaptic neurons and glial cellse
57
Q

what neurotransmitter do pyramidal neurons use?

A

glutamate

58
Q

how is GABA synthesised?

A

it is synthesised from glutamate from glutamate decarboxylase
it is metabolised by GABA transaminase

59
Q

what enzyme is GABA metabolised by?

A

GABA transaminase

60
Q

how is GABA stored?

A

it is actively transported into synaptic vescicles by vescicular GABA transporter

61
Q

describe the reuptake of GABA

A

its reuptake is by the GABA transporter into the pre and post synaptic membrane and astrocytes

62
Q

describe GABA pathways in the cerebral cortex

A

in the cerebral cortex GABAergic interneurons provide feedforward inhibition loops

63
Q

how is GABA linked to epilepsy

A

inhibition of GABA receptors has been found to induce seizures

64
Q

outline the synthesis, storage and reuptake of glycine

A
  • synthesised from L-serine by serine hydroxymethyltransferase
  • transported into synaptic vescicles via H+ dependent vesicular inhibatory amino acid transporter
  • release and reuptake is similar to GABA
65
Q

describe the function and pathology of glycine

A
  • major inhibitory neurotransmitter, particuarly in the brain and spinal chord
  • critical for regulation of motor neurons
  • involved in the retina, auditory system and sensory system
  • mutation in glycine receptor causes hyperplexia and startle reflex
66
Q

describe acetylcholine

A
  • excitatory neurotransmitter
  • is the transmitter at the neuromuscular junction
  • ionotropic receptors and g protein coupled receptors
67
Q

what is the synthesis storage and reuptake of acetylcholine

A

synthesised by choline acetyl transferase from choline to acetylcholine

transported into vescicles by vescicular Ach transporter

metabolised in the synapse by acetylcholinsterase to acetate and choline

choline is taken back into the presynaptic terminals by a choline carrier

68
Q

what is a cholinergic projection?

A

from the basal ganglia to the cerebral cortex and hippocampus

they have a role in cognitive function and are critical i memory

69
Q

what acteylcholineric receptors have been implicated in diseases?

A

muscarinic acetylcholinic receptors have been implicated in alzheimers disease, parkinsons and schizophrenia

nicotinic acteylcholine receptors have been implicated in pain, neurodegeneration and drug dependency

70
Q

what type of recetors di neuropeptides have

A

g protein coupled

71
Q

what is the synthesis of neuropeptides?

A
  • they are enzymatically cleaved from larger neuropeptide receptors in the endoplasmic reticulum
  • they are then transferred to the golgi apparatus for vesicular packaging and trafficked to the presynaptic terminal for release
72
Q

how are neuropeptides metabolised

A

they are metabolised by peptidases in the extracellular space

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