Exam 2 Flashcards
What are the 3 catecholamine neurotransmitters?
Dopamine, epinephrine, and norepinephrine
Why are catecholamines named the way they are?
They have a catechol nucleus with an additional amine group attached.
Most neurotransmitters are derived from ______ ______.
Amino acids
What is the amino acid precursor for all 3 catecholamine NTs?
Tyrosine (non-essential amino acid the body can make without food). Tyrosine is derived from the essential amino acid phenylalanine.
What are the derivatives of each catecholamine NT?
Dopamine is made from tyrosine. Norepinephrine is CNS version of epinephrine and is derived from dopamine. Epinephrine is adrenaline made in the adrenal glands. It is deprived from norepinephrine.
Describe the enzymes and groups added/removed to get tyrosine to DOPA, then dopamine, then to norepinephrine.
- Tyrosine converted to DOPA via tyrosine hydroxylase (TH) enzyme. A hydroxyl (-OH) group is added.
- DOPA is immediate precursor to dopamine. DOPA is converted to dopamine via the enzyme aromatic amino acid decarboxylase (AADC). Removes carboxylic acid (-COOH) from molecule.
- Dopamine converted to norepinephrine via enzyme dopamine Beta-hydroxylase (DBH). Adds a hydroxyl group.
Norepinephrine is then N-methylated in chromaffin tissue to become epinephrine via the enzyme phenyl-ethanonolamine-N-methyltrasnferase (PNMT). Adds a methyl group (-CH3) to NE.
After catecholamines are produced, what transporter slurps them up and stores them in a vesicle?
The Vesicular Monoamine Transporter-2 (VMAT2) is an active transporter that slurps up dopamine and NE to be stored at high concentrations within the neuron.
How is catecholamine release regulated by a negative feedback system?
Catecholamine release is inhibited by autoreceptors on neuron cells bodies, terminals, and dendrites. When autoreceptors sense enough NE or dopamine has been released from pre-synaptic neuron, they open up K+ channels and they flow out of the cell to hyperpolarize and stop the action potential. This change reduces the influx of calcium and vesicle exocytosis of these NT. Dopamine transporter then slurps dopamine back up into the presynaptic cleft. Dopamine can also be broken down in the synaptic cleft and presynaptic membrane.
What enzyme breaks down catecholamines in the synaptic cleft?
Monoamine oxidase breaks down these NTs!
What are monoamine oxidase inhibitors?
These were the first drug class used to treat depression but is not widely used today. This drug stopped the breakdown of dopamine and NE in the CNS. This inhibition causes the activity of dopamine and NE to increase. Increase in concentration of dopamine and NE in the limbic system is good for mood disorders.
What are the main 3 areas where dopamine is made in the brain?
- Nigrostriatal tract- axons in the substantia nigra (on top of brainstem in midbrain) extend to the basal ganglia
- Mesolimbic dopamine pathway- from the ventral tegmental area to various structures in the limbic system.
- Mesocortical dopamine pathway- starts in ventral tegmental area but axons go up to the prefrontal cortex.
Loss of dopaminergic neurons in what brain area leads to Parkinson’s disease?
Substantia nigra dies away during Parkinson’s disease.
What are characteristics of the nigrostriatal tract in dopamine production?
This tract is right on top of the brainstem. This pathway facilitates voluntary movement. Loss of dopamine neurons here results in Parkinson’s disease.
What are characteristics of the mesolimbic dopamine pathway in dopamine production?
Arises from the ventral tegmental area (right next to substantia nigra) and goes to various structures within the limbic system. This is thought to be the PRIMARY reward pathway. Drugs of abuse totally hijack this pathway.
What are characteristics of the mesocortical dopamine pathway in dopamine production?
Dopaminergic neurons starting in the ventral tegmental area but leading into the prefrontal cortex. This is also a reward pathway that can contribute to addiction. This is also the pathways that stimulants work through.
What happens to dopamine receptors in the brain of heavy coke or alcohol users?
When dopamine receptors are overstimulated by lots of dopamine, they will down regulate to have less receptors. This is why drug and alcohol addicts have less dopamine receptors. This then causes more of the drug to be consumed to feel the same effect since there are less receptors.
There are 5 types of dopamine receptors. All of which are ______________.
Metabotropic. All interact with G proteins and function via second messengers.
Where is epinephrine secreted from?
Secreted from the adrenal glands in response to sympathetic nervous system activation.
What are some basic functions of epinephrine?
Short-term stress hormone that prepares the body for strenuous activity. It causes breathing rate to increase, blood flow to muscles to increase, increased heart rate, pupils dilate, and more.
What are other common terms used when referring to norepinephrine?
Noreadrenaline and noradrengeric
How does the epi-pen work?
Local injection of epinephrine that reaches general circulation. Causes relaxation of airways, increase vasoconstriction to reduce swelling and increases heart rate to increase oxygen intake.
Where is norepinephrine made in the CNS?
Locus coeruleus in the pons is the main collection of NE neurons. They are in the hindbrain with axons that extend throughout the brain and spinal cord.
Norepinephrine receptors have two subtypes. Both of these receptors are _____________.
Metabotropic
Why is the neurotransmitter Acetylcholine named like it is?
It is an acetyl group attached to a choline group. It is a NT derived from nutrients and not amino acids.
What is Chantix?
This is a partial agonist of the nicotinic acetylcholine receptor.
What neurotransmitter is important in Alzheimer’s disease?
Acetylcholine
How is acetylcholine made?
Ach is formed from choline (consumed from foods like meat, eggs, veggies) and acetyl coenzyme A (made during sugar metabolism). Choline acetyltransferase is the enzyme that takes the acetyl group and places it onto the choline to make acetylcholine.
How and where is acetylcholine stored?
Ach is stored in vesicles at axon terminals. The vesicular ACh transporter (VAChT) is the transporter that places ACh into vesicles.
How is acetylcholine inactivated?
Acetylcholine is broken down into choline and acetic acid via the enzyme acetylcholinesterase (AChE). This enzyme is found in presynaptic and postsynaptic cells. Choline left in the cleft after breakdown is taken back into the cholinergic nerve terminal by a choline transporter. There is no ACh reuptake pump!
What is the first line treatment for Alzheimer’s disease?
A reversible inhibitor of the acetylcholinesterase enzyme allowing ACh to hang out longer and exert its effects.
How is glutamate created?
Start with the non-essential amino acids glutamine since cells produce a lot of this during the Krebs cycle. The enzyme glutaminase converts glutamine to glutamate via cleaving off NH2 group,
Describe the steps of glutamate NT release.
- Glutamine transporter picks up glutamine from the extracellular space and slurps it into the presynaptic neuron.
- Glutamine is converted to glutamate within neuron by enzyme glutaminase.
- Vesicular glutamate transporter then sucks up glutamate into vesicle to be stored for later release.
- NTs is released and binds and actions exerted. Once in synaptic cleft, a nearby astrocyte with an excitatory amino acid transporter (EAAT) slurps up glutamate from the cleft.
- Glutamate is instantly converted back to glutamine via glutamine synthetase in the astrocyte.
- Glutamine is kicked out of the astrocyte into the extracellular space and can be sucked up by a nearby neuron for the process to start over again.
What are the 3 types of ionotropic glutamate receptors?
- AMPA receptor- flow of Na+ into the cell to depolarize it
- NMDA receptor- receptor that alcohol inhibits. Let sodium and calcium flow into cell to depolarize.
- Kainate receptor- flow of Na+ into the cell.
Describe memory formation in relation to NMDA and AMPA ionotropic glutamate receptors.
At rest, NMDA receptors are blocked by a magnesium ion acting like a plug in a bathtub. When an action stimulates the hippocampus to form memories, these receptors are activated. Glutamate binds to AMPA receptors which opens up the ion channel and Na+ flows into the neuron and it is depolarized. That slight stimulation of Na+ rushing in depolarizes nearby membranes causing the shape of the NMDA receptor to change and magnesium pops out. Glutamate can then bind to the NMDA receptor. This allows Na+ and Ca2+ to flow into the neuron. The influx of Ca2+ ions through NMDA activates several protein kinases resulting in long-term potentiation of memory formation.
How is GABA made?
GABA is made from glutamate. Glutamate is converted to GABA via glutamic acid decarboxylase (GAD) enzyme. GABA neurons will have glutaminase and GAD enzymes!
Describe the steps of GABA release.
- Glutamine in extracellular space is slurped up by glutamine transporter into presynaptic neuron.
- Glutamine is converted to glutamate via glutaminase enzyme.
- Glutamate is converted to GABA via glutamic acid decarboxylase (GAD).
- GABA is transported into synaptic vesicles for storage by vesicular GABA transporters (VGAT).
- GABA is released and binds to receptors and is in the synaptic cleft. The GABA transporter (GAT) on nearby astrocytes slurps GABA back into its astrocyte.
- Astrocyte converts GABA to glutamate by enzyme GABA transaminase.
- Glutamate is converted to glutamine via enzyme glutamine synthetase which is pumped out of astrocyte into extracellular space for process to begin again.
What is the affect of positive allosteric modulators binding to GABA receptors?
Positive allosteric modulators cause a conformational change of the GABA receptor leading to an INCREASED affinity of endogenous GABA. For example, alcohol and benzos activate GABA A receptors by allowing GABA to better activate the receptor.
How does tryptophan enter into the CNS?
It needs to be actively transported into the CNS via the large amino acid transporter (LAT). It competes for entry into CNS with other amino acids.
Where are serotonergic neurons found in the brain?
In the CNS, 5-HT producing neurons are in clusters. In the raphe nuceli of the midbrain, pons, and medulla. These clusters project broadly and are mostly inhibitory.
How is serotonin made from tryptophan?
Tryptophan is converted to 5-HTP via the enzyme tryptophan hydroxylase adding an -OH group. 5-HTP is then converted to 5-HT via aromatic L-amino acid decarboxylase (AADC) enzyme by removing a carboxyl group from side chain.
How is serotonin released and taken back up?
Tryptophan is converted to serotonin within the presynaptic neuron. Serotonin is slurped into vesicles for storage via the vesicular monoamine transporter (VMAT2). Serotonin is released into cleft and then taken back up via the SERT/ 5-HT transporter into the presynaptic terminal. Some serotonin is broken down while others are recycled. Monoamine oxidase is the enzyme that breaks down serotonin within the cleft.
Describe the 5-HT 1A autoreceptor for serotonin.
5-HT 1A is the serotonin autoreceptor. It is an inhibitory G protein receptor. When serotonin binds to this receptor, K+ channels open and leave cell to hyperpolarize it.
Describe the 5-HT 2A serotonin receptor.
This is a Gq receptor meaning it likely activates. When serotonin binds to this receptor activity in post-synaptic neurons bringing them closer to firing through the IP3 second messenger system. This results in increased calcium in postsynaptic cells that activate protein kinase C.
