Neurotransmitters Flashcards
What is a monoamine?
A class of NTs made by modifying a single amino acid
What are examples of monoamines?
Epinephrine, norepinephrine, dopamine, serotonin, histamine
Where do you find norepinephrine?
Locus ceruleus
What is norepinephrine associated with?
Wakefulness/alertness
Where do you find epinephrine?
Medulla
How are norepinephrine and epinephrine derived?
Tyrosine -> dopamine -> norepinephrine -> epinephrine
How are norepinephrine and epinephrine made?
- Tyrosine to dopamine via tyrosine hydroxylase
- Moved to vesicles where NE is created
- NE leaves vesicles and is converted to epi
- Epi moved into vesicles
What transporter moves epi and NE into vesicles?
VMAT 1 & 2
How are the actions of epi/NE limited?
Reuptake or enzymatic degradation via MAO or COMT
Where do you find dopamine?
Basal ganglia and hypothalamus/limbic system
What is dopamine involved in?
Motor control and endocrine/emotional control
How is dopamine made?
From tyrosine via tyrosine hydroxylase
How are dopamine’s actions limited?
Reuptake or catabolism by MAO and COMT
What does dopamine bind to?
Metabotropic receptors connected to G proteins.
D1 and D5 increase cAMP (in brain = neuron excitation)
D2, D3, and D4 decrease cAMP (=inhibits cell)
Where do you find serotonin?
Brainstem raphe nuclei
What is serotonin involved in?
Mood (hypothalamus/limbic system) and motor activity modification (cerebellum)
How is serotonin made?
Derived from tryptophan via tryptophan hydroxylase
How are serotonin’s actions limited?
Reuptake or catabolism by MAO and COMT
What does serotonin bind to?
5HT3 - area postrema (chemotactic trigger zone = vomiting)
5HT6 - anti-depressant effect
Where do you find histamine?
Tuberomammillary nucleus of hypothalamus
What is histamine involved in?
Wakefulness
How is histamine made?
Derived from histidine via histidine decarboxylase
How are histamine’s actions limited?
Reuptake or catabolism by diamine oxidase (DAO) and COMT
What does histamine bind to?
H1 - PLC activation (wakefulness)
H2 - increase cAMP
H3 - decrease histamine release
Where is Ach made?
Striatum of basal ganglia, midbrain, and pons
What does Ach function in?
Striatum: voluntary motion
Midbrain/pons: baseline excitation to cortex and REM sleep
What Ach receptors are in the CNS?
M1 (Gq increases Ca2+)
M4 (Gi decreases cAMP)
M5 (Gq increases Ca2+)
What are the two major inhibitory amino acids in the CNS?
GABA and glycine
What are GABA and glycine critical in?
Consciousness, motor control, vision (retina)
How is GABA made?
Synthesized from glutamate via glutamate decarboxylase, transported into vesicles via VGAT, removed from synapse via GAT1 (presynaptic terminal) and GAT2 (surrounding glial cells)
What does GABA bind to?
GABA A receptors that produce IPSP in adult neurons. Some are extra-synaptic receptors that function as a site of action for anesthetics
GABA B receptors: presynaptically regulate GABA release, postsynaptically inhibit postsynaptic cell
Where is glycine found?
Spinal cord, medulla
What does glycine function to do?
Mediates spinal inhibitions
How is glycine removed from synapses?
GAT (like GABA)
What does glycine bind to?
GlyR receptors, influx of chloride leads to IPSP
Where are purines found?
ATP, ADP, adenosine found everywhere in CNS. Specifically in cortex, cerebellum, hippocampus, and basal ganglia
What do purines bind to?
P1: presynaptic = sleep induction, inhibition of neural function. Postsynaptic = inhibition of NT release
P2: P2X and P2Y (learning/memory)
What are some examples of peptide transmitters?
Opioids, tachykinins, cholecystokinin, somatostatin
What types of opioids are there?
Endorphins, enkephalins, dynorphins, nociceptin
What are the precursor molecules to opioids?
Proopiomelanocortinin (POMC), pro-enkephalin, pro-dynorphin, orphanin FQ
How are opioids made?
Via standard protein synthesis
How are the effects of opioids controlled?
Reuptake and enzymatic destruction
What do opioids bind to?
Mu receptors - analgesia, respiratory depression, euphoria, constipation, sedation
Kappa receptors - analgesia, dysphoria (unpleasant)
Delta receptors - analgesia
All are metabotropic
What are the endogenous cannabinoids?
Anandamide and 2AG
Where do you find endocannabinoids?
Basal ganglia (mood, motor), spinal cord (modulate nociception), cortex (neuroprotection)
How are endocannabinoids synthesized?
Derived from membrane lipids, synthesized in presynaptic terminal
What do endocannabinoids bind to?
CB1 on presynaptic terminals in CNS
CB2 on microglia (anti-inflammatory)
How are endocannabinoids degraded?
Hydrolyzed or oxidized
What are the excitatory amino acids?
Glutamate and aspartate
What do EAAs bind to?
NMDA receptor (influx of calcium) with modulatory glycine binding site (required as co-agonist), modulatory magnesium binding site (blocks the channel), modulatory PCP binding site (blocks channel) Non-NMDA receptors (AMPA and kainate)
