Topic 4 (neurotransmitters and receptors) Flashcards
what are 6 types of receptors?
photoreceptor (light) mechanoreceptor (touch) t cell receptor (immunology) complement receptor (immunology) binding site receptor (pharmacology) drug/toxin target receptor (pharmacology) neurotransmitter/neurohormone receptor
what are 3 possible locations for receptors with examples
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
how many subunits are in nicotinic receptors?
5 subunits, each which 4 transmembrane domains
what are 4 examples of nicotinic receptors?
Nicotinic acetylcholine receptors
GABAa receptors
5HT3 (Serotonin) receptors
Glycine receptors
how many subunits are in ionotropic glutamate receptors?
4, each with 3 transmembrane domains
how do ligands bind to ionotropic glutamate receptors?
the ligand binding domain acts like a clamshell when the ligand binds
what are 3 examples of ionotropic glutamate receptors?
NMDA receptor
AMPA receptor
Kainate receptor
name 5 excitatory ligand gated ion channels
acetylcholine receptor serotonin receptor NMDA receptor AMPA receptor Kainate receptor
name 2 inhibitory ligand gated ion channels
GABAa, Glycine
how many transmembrane domains are g protein coupled receptors made of?
7
where does the neurotransmitter bind to in rhodopsin like g-protein coupled receptors
the ligand binds to the transmembrane domains, either extracellularly or within the membrane
what are 6 examples of rhodopsin like G protein coupled receptors?
muscarinic acetylcholine receptors noroadrenergic receptors opioid receptors serotonergic receptors (except 5ht3) neuropeptide y receptors
where does the ligand bind in metabotropic glutamate receptors?
theres a large n terminus where the ligand binds like a venus fly trap
what are 2 examples of metabotropic glutamate receptor like receptors?
GABAb
Metabotropic glutamate receptors
what GABA receptors are ionotropic or metabotropic
GABAa and GABAc are ionotropic
GABAb is metabotropic
How does the g protein coupled receptor activate the g protein?
- GDP is bound to the alpha subunit of the G protein
- Receptor activation causes GDP to be exchanged for GTP causing the alpha subunit (with the gtp) to dissociate from the B,Y subunit
- 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
name 3 types of neurotransmitters with examples?
MONOAMINES
- dopamine
- noradrenaline
- serotonin
AMINO ACIDS
- Glutamate
- GABA
- Glycine
NEUROPEPTIDES
Name 5 ligand gated ion channel neurotransmitters
EXCITATORY
- serotonin
- glutamate
- acetylcholine
INHIBITORY
- GABA
- Glycine
Name 7 examples of G protein coupled receptor neurotransmitters
- dopamine
- noradrenaline
- serotonin
- Glutamate
- GABA
- Acetylcholine
- -Neuropeptides
Name 4 examples of neurotransmitters with both ligand gated ion channels and g protein coupled receptors
- serotonin
- glutamate
- gaba
- acetylcholine
Name 3 neurotransmitters that are G protein coupled receptors only
dopamine
noradrenaline
neuropeptides
name one neurotransmitter which only has ligand gated ion channels
Glycine
Descripe DOPAMINE
- 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
Describe NORADRENALINE
- 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
Describe SEROTONIN (5HT)
- it has modulatory actions via G protein coupled receptors (except 5HT3)
- its involved in sleep, appetite, thermoregulation, pain, depression, anxiety, OCD, schizophrenia
Outline the monoamine transmission pathway
- synthesised in the neuron
- stored in vesicles via active transport (vescicular monoamine transporter)
- released from the nerve terminals via excocytosis
- Acts on target receptor
- Removed from the synaptic cleft via monoamine transporter into glial cells or presynaptic neuron
outline monoamine oxidase
- 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
Outline COMT (Catechol-o-methyl transferase)
- it metabolises monoamines
- its located in post synaptic neurons and glia
- it has soluble or membrane bound forms
- it metabolises dopamine or noradrenaline
what are 4 dopaminergic pathway’s
Nigrostriatal pathway
Mesolimbic pathway
Mesocortical pathway
Tuberoinfundibular pathway
what is the pathway, role and pathology of the nigrostriatal pathway
- from the substantia nigra to the striatum
- role is in movement
- degenerates in parkinsons disease
What is the pathway, role and pathology of the mesolimbic pathway
- 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
what is the pathway role and pathology of the mesocortical pathway
- it goes from the ventral tegmental area to the cortex
- its involved in cognition, motivation and emotion
- it is implicated in schizophrenia
What is the pathway and role of the tuberoinfundibular pathway
- it goes from the hypothalamus to the medium eminence
- its involved in prolactin release from the pituitary gland
How is dopamine syntheised
- tyrosine is converted to L-dopa by tyrosine hydroxylase
- Ldopa then gets converted to dopamine by aromatic l-amino acid decarboxylase
how is dopamine stored?
its stored in vescicles by vesicular monoamine transporter
how is dopamine released?
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
what dopamine receptors are there
- 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
describe dopamine reuptake
dopamine is taken up into the axon terminal by the dopamine active transporter (DAT)
this cotransports dopamine with chloride and sodium ions
What can dopamine get degraded into?
Aldehyde Dehydrogenase or 2-methoxydopamine
Either of these can then be further degraded to homovaillic acid
what are the three enzymes involved in degrading dopamine
monoamine oxidase
catechyl-o-methyltransferase
aldehyde dehydrogenase
outline how drugs afftect the dopamine system
dont need to memorise all drugs
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
outline the synthesis of noradrenaline
synthesised from dopamine
by dopamine-b-hydroxylase (found only in noradrenic neurons)
how is noradrenaline stored
- 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
what are the two noradrenergic pathways?
locus coeruleus nuclei
caudal raphe nuclei
where does the noradrenergic locus correleus nuclei project to?
frontal cortex, thalamus, hypothalamus, limbic system, cerebellum
where do noradrenergic neurons from the caudal raphe nuclei project to?
ascend to the amygdala
Descend to the spinal chord
how are noradrenergic pathways linked to pathology?
low NA transmission is linked with depression
noradrenergic pathways can affect blood pressure
how is serotonin synthesised
from tryptophan to 5hydroxytryptophan to serotonin
using the enzymes tryptophan hydroxylase and aromatic L-amino acid decarboxylase
Describe the serotonergic rostral and caudal raphe nuclei pathways
- 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
how is serotonin implicated in pathology
- low serotonin involved in depression
- different receptors involved in migraine, anxiety, emesis and psychosis
describe glutamate
- 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
Describe GABA
- gaba is the major inhibitatory neurotransmitter
- its ionotropic receptor is GABAa
- its metabotropic receptor is GABAb
describe glycine
- inhibitory ionotropic receptors
how is glutamate synthesised?
- synthesised in the brain from the metabolism of glucose in neurons and glutamine in astrocytes
how is glutamate stored?
- it is stored in synaptic vescicles
- these vescicles actively accumulate glutamate via the vesicular glutamate transporter
describe the reuptake of glutamate
- glutamate is taken up by excitatory amino acid transporters on presynaptic neurons and glial cellse
what neurotransmitter do pyramidal neurons use?
glutamate
how is GABA synthesised?
it is synthesised from glutamate from glutamate decarboxylase
it is metabolised by GABA transaminase
what enzyme is GABA metabolised by?
GABA transaminase
how is GABA stored?
it is actively transported into synaptic vescicles by vescicular GABA transporter
describe the reuptake of GABA
its reuptake is by the GABA transporter into the pre and post synaptic membrane and astrocytes
describe GABA pathways in the cerebral cortex
in the cerebral cortex GABAergic interneurons provide feedforward inhibition loops
how is GABA linked to epilepsy
inhibition of GABA receptors has been found to induce seizures
outline the synthesis, storage and reuptake of glycine
- 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
describe the function and pathology of glycine
- 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
describe acetylcholine
- excitatory neurotransmitter
- is the transmitter at the neuromuscular junction
- ionotropic receptors and g protein coupled receptors
what is the synthesis storage and reuptake of acetylcholine
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
what is a cholinergic projection?
from the basal ganglia to the cerebral cortex and hippocampus
they have a role in cognitive function and are critical i memory
what acteylcholineric receptors have been implicated in diseases?
muscarinic acetylcholinic receptors have been implicated in alzheimers disease, parkinsons and schizophrenia
nicotinic acteylcholine receptors have been implicated in pain, neurodegeneration and drug dependency
what type of recetors di neuropeptides have
g protein coupled
what is the synthesis of neuropeptides?
- 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
how are neuropeptides metabolised
they are metabolised by peptidases in the extracellular space
