DSA: Neurotransmitter Systems (Karius) Flashcards
What are the functions of the dopamine receptors we know of?
D1 and D2 funcitons in the substantia nigra.
D3 is involved in the pleasure and reward system.
Where is norepinephrine located in the CNS?
Locus ceruleus
(spelling varies)
What is the function of the tuberinfundibular pathway?
This is the pathway in which dopamine can supress prolactin.
Runs from the hypothalamus to the anterior pituitary.
What symptom is a consequence of NO synthesis in the pons?
Apneusis
What enzyme converts norepinephrine into epinephrine?
PNMT
(Phenylethanolamine-N-methyl transferase)
What is the function of the mesocortical dopaminergic pathway?
Crucial to attention and higher consciousness.
Dysfunction leading to schizophrenia.
What are the two endocannabinoids?
Anandamide
2AG (2-arachidonylglycerol)
Where is serotonin located in the CNS?
In the midline raphe nuclei.
What is directly caused by activation of the NMDA channel?
What molecules are required for NMDA channel activation?
Opening of a calcium channel.
Glutamate or aspartate and glycine.
What are the receptors for dopamine?
What G proteins are they coupled to?
D1 through D5
D1 and D5 are coupled to Gs
D2, D3, and D4, are coupled to Gi
What is the function of serotonin in the CNS?
Serotonin in the midline raphe nuclei functions in attention and mood - as well as pain transmission in the spinal cord.
Disruptions are associated with depresion.
What are the two enzymes that reclaim GABA, and where are they located?
GAT1 is found on the presynaptic terminal for direct recycling.
GAT2 is found on glial cells, where GABA is converted backwards into glutamine, and is then sent to the presynaptic neuron.
What enzyme clears histamine from the synapse?
Diamine oxidase
How might anesthetics cause unconsciousness?
They have binding sites on the GABAA receptor, causing an influx of Cl-.
They also have binding sites on glycine receptors, allowing an influx of chloride as well.
What transporter class moves dopamine into vesicles?
Which specific transporter is found in the neurons?
VMATs move dopamine into vesicles.
VMAT 2 is found in monoamine releasing neurons. (Whereas VMAT 1 is found in the adrenal medulla)
What are the three opiod receptors?
μ-receptor
κ-receptor
δ-receptor
What are the two types of non-NMDA receptors, and what are the characteristics of each?
- AMPA receptors
- Glutamate and aspartate are the endogenous ligands
- There is a binding site for benzodiazepines on the AMPA receptor (as well as on the GABA receptor) which blocks them, decreasing sodium influx. This causes the sedative effect.
- Kainate receptors
- Simply binds to glutamate or aspartate and lets sodium in. No other cool facts here – except that it’s exogenous ligand “kainate” was originally derived from seaweed, and is called “Kainin-sou” in japan. #Darrenfacts
What enzyme clears serotonin from the synapse?
MAO, just like the catecholamines.
What GABA receptor is ionotropic, and what ion is admitted?
GABAA is ionotropic, and lets in chloride.
What two enzymes remove dopamine, epinephrine, and norepinephrine from the synaptic terminal?
MAO (monoamine oxidase)
COMT (Catechol-O-methyl Transferase)
(Mostly MAO in the CNS, whereas COMT is more common in the PNS)
What is the P1 purine receptor specific for?
Is it ionotropic or metabotropic?
What are its functions?
P1 is specific for adenosine.
Presynaptic P1 receptors inhibit NT release. Postsynaptic receptors inhibit neural function, and are specifically associated with sleep induction.
(Caffeine blocks P1 adenosine receptors)
How are excitatory amino acids removed from the synapse?
Glial cells take them up and convert them back down to a less toxic molecule (eg: glutamate to glutamine).
What amino acid is synthesized into histamine?
Histidine
What three receptor types are there for norepinephrine and epinephrine?
What G proteins are they coupled to?
Alpha 1 = Gq
Alpha 2 = Gi
Beta = Gs
What is the relationship between NMDA receptors and NO production?
NMDA allows calcium into cells, where it can bind to calcineurin. This Ca2+/calcineurin complex activates NO synthase.
What amino acid are norepinephrine and epinephrine derived from?
Tyrosine
What 4 places is dopamine heavily featured in the CNS?
Substantia nigra
Mesolimbic pathway
Mesocortical pathway
Tuberinfundibular pathway
What are the locations of the GABAB receptor, and what are their functions?
GABAB receptors are metabotropic, and couple with Gi/Go.
Gi opens a K+ channel, which hyperpolarizes the membrane (inhibitory)
Go decreases calcium influx.
By what two mechanisms can benzodiazepines cause sedation?
They have binding sites on GABAA receptors - which lets in chloride.
They have binding sites on non-NMDA AMPA receptor, which blocks it from letting in sodium (anti-excitatory).
Where is histamine found in the CNS?
In the tuberomamillary body.
Where are the two cannabinoid receptors found?
What are their functions in that area?
CB1 is found in the nervous system and is coupled to Gi proteins (metabotropic)
CB2 is found in the immune system, and is involved in neuroprotection (and we don’t care about it.)
Where is acetylcholine located in the CNS?
What is its function?
Located in the brainstem. - Serves to promote arousal.
Also located in the striatum of the basal ganglia. - Serves in motor control.
What enzyme transports GABA into vesicles?
VGAT
Vesicular GABA transporter protein
Which inhibitory amino acid neurotransmitter is more localized to the higher CNS, and which is localized to the lower CNS?
GABA is more localized to the higher CNS, and Glycine is localized to the lower CNS and brain stem.
When does magnesium block NMDA channels?
When the neuron is at resting membrane potential.
What two enzymes destroy opioid peptides?
Enkephalinase
Aminopeptidase
What is the direct function of μ receptors, vs κ and δ receptors?
μ receptors increase potassium efflux
κ and δ receptors decrease calcium influx
What are the P2 receptors specific for?
What are the two types, and their differences?
P2 receptors are specific for ADP and ATP (other nucleotides may bind).
P2X is ionotropic and binds ATP only.
P2Y is metabotropic (Gs/Gq receptors) and can bind the other ligands.
What amino acid is synthesized into GABA?
Glutamate
What are the exitatory amino acids?
Glutamate and aspartate.
What are the three locations of action of endocannabinoids we are responsible for, and their functions in those regions?
Basal ganglia - mood and motor performance
Spinal cord - nocioception
Cortx - neuroprotection
What functions (besides vasodilation) does NO have in the brain?
Long term potentiation of memory in the hippocampus and cerebellum.
Cardiovascular and respiratory control in the pons and medulla.
What is the rate limiting step in the synthesis of serotonin?
Tryptophan hydroxylase
What are the three histamine receptors, and what are their functions?
H3 is a feedback receptor primarily in charge of conveying when enough histamine has been released.
H1 and H2 actually perform the functions of histamine: wakefulness via the locus ceruleus that norepinephrine also interacts with.
What is the function of the mesolimbic dopaminergic pathway?
Reward system.
Runs from the ventral tegmental area to the nucleus accumbens.
What receptors exist for glycine?
What are the functions?
Glycine only has an ionotropic “glycine receptor.”
It allows the entrance of Cl- as an inhibitory effect.
Is the NMDA receptor linked calcium channel voltage gated or ligand gated?
Both!
The glycine/EAA requirement means it is ligand gated, and the magnesium blockade at resting membrane potential means its voltage gated.
What precursor are the endocannabinoids derived from?
Arachidonic acid
What are the four precursor molecules for opioid peptides?
Pro-opiomelanocortin
Pro-enkephalin
Pro-dynorphin
Orphanin FQ
(Pay attention to the bolded precursors)
What are the three Serotonin receptors we care about, and what are their functions?
5-HT3: associated with vomiting.
5-HT6: affinity for anti-depressants.
5-HT2c: may play a role in maintaining body weight and preventing seizures.
What is the function of the locus ceruleus?
Norepinephrine in this area plays a role in wakefulness.
Are opiod receptors metabotropic or ionotropic?
Metabotropic
(They are coupled with Gi/Go proteins)
How is acetylcholine removed from the synapse?
Acetylcholinesterase
What enzyme shuttles acetylcholine into vesicles?
VAchT
(Vesicular acetylcholine transporters)
What are the three metabotropic excitatory amino acid receptors?
What G proteins do they couple with?
Groups 1, 2, and 3.
Group 1 couples with Gq
Group 2 and 3 couples with Gi
What is the rate limiting step in epinephrine synthesis?
Tyrosine hydroxylase.
Which opiod receptor causes euphoria?
The μ-receptor
How is glycine removed from the synapse?
Via GAT1/GAT2 proteins - same as GABA
What ion enters the postsynaptic cell after activation of a nicotinic acetylcholine receptor?
Primarily sodium
What is the mechanism of action of Strychnine?
Strychnine is a glycine antagonist, causing inactivation of the inactivator, pathologically increasing certain processes.
What is the rate limiting step in GABA synthesis?
Glutamate decarboxylase
What are the functions of NMDA receptors?
Short and long term memory formation, as well as brain plasticity.
