Chapter 6: Neurotransmitter Systems Flashcards
Those receptors which respond to the transmitter acetylcholine and are mostly parasympathetic.
Cholinergic
a neurotransmitter in your brain and spinal cord; Increases alertness, arousal and attention. Constricts blood vessels, which helps maintain blood pressure in times of stress. Affects your sleep-wake cycle, mood and memory.
Noradrenergic (NE)/ Norepinephrine
Stimulate the nerves in your body’s sympathetic nervous system (SNS). This system helps regulate your body’s reaction to stress or emergency. During times of stress, the SNS releases chemical messengers from the adrenal gland. constrict blood vessels. open the airways leading to the lungs.
Adrenergic (EPI)/ Epinephrine
They’re a key type of drug for treating movement disorders, especially Parkinson’s disease; means “related to dopamine”. Acts on areas of the brain to give you feelings of pleasure, satisfaction and motivation. It also has a role to play in controlling memory, mood, sleep, learning, concentration, movement and other body functions.
Dopaminergic/ Dopamine (DA)
A type of ionotropic glutamate receptor; A glutamate-gated ion channels, present in a wide range of neuron types and in glial cells. Their main role is to mediate fast excitatory synaptic transmission; The number and subunit composition of these at synapses determines the dynamics of fast glutamatergic signalling.
AMPA receptor
A type of ionotropic glutamate receptor/ glutamate-gated ion channels; is a tetrameric ionotropic glutamate receptors; contributes to excitatory postsynaptic currents; require not only the neurotransmitter l-glutamate (l-Glu) but also external sodium and chloride ions for activation.
Kainate receptor
A type of ionotropic glutamate receptor/ Glutamate-gated cation channels that allow for an increase of calcium permeability. Channel activation of these receptors is a result of the binding of two co agonists, glycine and glutamate. Overactivation of these receptors, causing excessive influx of Ca2+ can lead to excitotoxicity.
NMDA receptor
Defined by the pharmacological characteristics of the site and is based on the availability of selective agonists and antagonists for the subtypes.
Receptor Subtype
It is a coincidence detector meaning its both a ligand and voltage gates ion channel; mediates long-term potential (LTP) .
NMDA receptors
Integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane; IONOTROPIC and allows fast synaptic transmission; membrane protein channels that only open when a chemical (neurotransmitter) released from the presynaptic neuron bind to them. depolarization. when the membrane potential of a cell becomes less negative.
Ligand-gated channel
integral membrane proteins that enable the passage of selected inorganic ions across cell membranes. They open and close in response to changes in transmembrane voltage, and play a key role in electrical signaling by excitable cells such as neurons.
Voltage-gated Channel
Directly gate ion flow into cells, leading to either excitatory or inhibitory responses in postsynaptic neurons. Ex: ligand-gated ion channels and nACH receptors.
Ionotropic Receptors
They are pentamers (an entity composed of five sub-units);
In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction.
nACH receptors
Has 2 main categories: 1) transmitter-gated ion (inotropic) channels. 2) g-coupled receptors (metabotropic).
Neurotransmitter Receptors
Act either directly or indirectly as signal transduction enzymes, or are linked to enzymes that have an extracellular domain recognizing a drug and an intracellular domain that catalyzes a biochemical response; require G proteins and second messengers to indirectly modulate ionic activity in neurons.
Metabotropic Receptors
The ability of a neuron to release multiple transmitters
Co-transmitters
Chief neurotransmitter of the parasympathetic nervous system; contracts smooth muscles, dilates blood vessels, increases bodily secretions, and slows heart rate; a neurotransmitter that plays a role in memory, learning, attention, arousal and involuntary muscle movement. Related to the issue of myasthenia gravis (autoimmune disorder caused by production of antibodies against cholinergic receptors at NMJ)
Acetylcholine (ACh)
specialized membrane-spanning proteins that assist in the movement of ions, peptides, small molecules, lipids and macromolecules across a biological membrane.
Transporter
The slowest step in a metabolic pathway or series of chemical reactions, which determines the overall rate of the other reactions in the pathway.
Rate-Limiting Step
Includes Dopamine, norepinephrine, and epinephrine. Synthesis in nerve terminal begins with the conditionally essential amino acid tyrosine. Packaged by synaptic vesicles; reuptake via plasma membrane transporters (DAT and NET)
Catecholamines
is the rate limiting enzyme in the pathway of Catecholamine synthesis; helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine.
Tyrosine Hydroxylase (TH)
an enzyme involved in the building (synthesis) of neurotransmitters (dopamine and serotonin); a vitamin B6-requiring enzyme that converts L-dopa to dopamine and 5-hydroxytryptophan to serotonin.
Aromatic Amino Acid Decarboxylase (AADC aka DOPA decarboxylase)
regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse.
Vesicular Monoamine transporter (VMAT2)
an enzyme responsible for the degradation (BREAKDOWN) of catecholamines, such as dopamine and norepinephrine.
Catechol-O-methyltransferase
involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain; an inhibitor.
Monoamine oxidase (MAO)
Chemical; controls mood, sleep, digestion, nausea, wound healing, bone health, blood clotting and sexual desire. It is a monoamine in the class of indoleamines. Synthesized in 2 steps. Related to a major class of antidepressants.
Serotonin (5-HT)
Converts tryptophan to 5-HTP; rate limiting step in the synthesis of serotonin. has 2 forms: TPH1 and TPH2
Tryptophan Hydroxylase (TPH)
Includes glutamate, glycine and GABA
Amino Acid Neurotransmitters
Synthesized by glucose; an excitatory neurotransmitter with several types of receptors found throughout the central nervous system, and it is important to memory, cognition, and mood regulation.
Glutamate
inhibitory neurotransmitter in the CNS; it slows down your brain by blocking specific signals in your central nervous system (your brain and spinal cord); related to epilepsy.
GABA
GAT-1 blocker; blocks reuptake of GABA from synaptic cleft.
Tiagabine
Inhibitor of GABA-T; prevents GABA metabolism
Vigabatrin
Co-transporters and uses ionic gradients as sources of energy. A collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes; EX: SERT, DAT, GAT.
Membrane Transporters
Counter-transporters and uses ionic gradients as sources of energy. Small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells.EX: VMAT
Vesicular Transporters
RETROGRADE Messengers (go from post to pre) and binds to CB1 receptors (brain) and CB2 (immune system). It is synthesized in the POST-synaptic nerve terminal.
Endocannabinoids
A gasotransmitter- not stored in vesicles. Synthesized from the amino acid Arginine. RETROGRADE MESSENGER.
Nitric Oxide (NO)
Not synthesized in the nerve terminal; released in nerve terminal via CA^2+ dependent exocytosis. It is synthesized in the SOMA.
Opioids
What is Acetylcholine (ACh)’s enzyme for synthesis?
ChAT
Where is Acetylcholine (ACh) synthesized?
presynaptic terminal
How is Acetylcholine (ACh) packaged into vesicles?
VAChT
What enzyme(s) will break down Acetylcholine (ACh)?
AChE
What is Acetylcholine (ACh)’s reuptake transporter?
Choline Transporter
Where is Glutamate synthesized?
presynaptic nerve terminal
How is Glutamate packaged into vesicles?
VGLUT
What is Glutamate’s reuptake transporter?
EAATs
What is GABA’s enzyme for synthesis?
GAD
Where is GABA synthesized?
presynaptic nerve terminal
How is GABA packaged into vesicles?
vGATs
What enzyme(s) will break down GABA?
GABA-T
What is GABA’s reuptake transporter?
GAT
What is Dopamine’s enzyme for synthesis?
TH, AADC
Where is Dopamine synthesized?
presynaptic nerve terminal
How is Dopamine packaged into vesicles?
VMAT 2
What enzyme(s) will break down Dopamine?
MAO, COMT
What is Dopamine’s reuptake transporter?
DAT, NET
What is Serotonin’s enzyme for synthesis?
TPH, AADC
Where is Serotonin synthesized?
presynaptic nerve terminal
How is Serotonin packaged into vesicles?
VMAT 2
What enzyme(s) will break down Serotonin?
MAO
What is Serotonin’s reuptake transporter?
SERT
What are the characteristics of Ionotropic receptors?
- Fast synaptic transmission
- Subunits come together to form a functional ion channel.
- Regulate flow of currents
- Differentiates between different ions
What are the characteristics of nACh Receptors (nicotinic recpetos)
- Nicotinic receptors are pentamers
- Different subunits combinations at NMJ & neuronal form
- ACh receptors
- Very few neuronal nAChs in brain— though some are located in brain reward system
What are the characteristics of Ionotropic Glutamate receptors?
- Three subtypes
- AMPA (agonist)
- Kainate (agonist)
- NMDA (agonist)
Do NMDA & AMPA coexist? What’s the difference?
Yes, they coexist in the neuronal membrane.
* AMPA when bound to glutamte will open up and allows sodium to flow into cell cause depolarization
* NMDA are permeable to Na+ & Ca++
Describe NMDA receptors
- Needs more than glutamate to bind in order to open
- Both ligand & voltage gated.
- **Ligand gate: Glutamate must be bound
- Voltage gate: at resting Vm, channel is blocked by Mg++**
- **Adjacent AMPA receptor channels mediate initial depolarization
** NMDA receptors and AMPA receptors typically coexist in the membrane. ** - Plays a vital role in learning and memory.
What is glutamate excitotoxicity?
- Glutamate can lesion any brain area if injected directly.
- **Prolonged depolarization of receptor neurons leads to death. **
Describe the GABAa Receptor
- When GABA binds, it causes a change and when it opens up, there is an influx of Cl- which causes an hyperization.
- GABA mediates most synaptic inhibition in CNS
- Inhibitory Cl- current leads to IPSP
- Made of different subunits.
Describe the characteristics of GPCRs
Not ion channels, they are monomeric proteins that contain seven transmembrane domains
* Slower, longer lasting, and more complex
* Modify ion channels
* Exert their effects via GTP-binding proteins
- heterotrimeric proteins: alpha, beta, gama
There are GPCRs for glutamte, ACh, Dopamine, and Serotonin
What is the difference between a G protein gated ion channel & effector protein enzyme?
- The ion channel diffuses along the membrane and this is known as the “short-cut pathway”
- **The enzyme synthesizes second messengers that are freely diffusible in the cytosol.
- First messenger is the neurotransmitter
**
- First messenger is the neurotransmitter
Describe the inactive vs active stages of GPCRs
Inactive:
* 3 subunits float in the membrane, Alpha is bound to GDP
Active:
* Bumps into activated receptor and exchanges GDP for GTP
* Alpha GTP and Beta influence effector proteins
* Alpha inactivates by slowly converting GTP to GDP.
* Alpha and Beta recombine to start the cycle again.
Describe protein kinases
- Transfer phosphate from ATP in cytosol to proteins - phosphorylation; determines whether channel is open or closed.
- Protein phosphatases remove the phosphate groups - dephosphorylation
Why GPCRs
A single NT can activate 10-20 G-proteins
- Advantage is signal amplification.
What is divergence and convergence?
Divergence:
One transmitter activates more than one receptor subtype —> greater postsynaptic response.
**Convergence:
**Different transmitters converge to affect same effector system**
