Neurotransmitters Flashcards
Two fast neurotransmitters are […] and they operate through […] receptors.
Glutamate (excitatory) and GABA (inhibitory)
Ligand-gated ion channels
Three slow neurotransmitters and neuromodulators are […] and they operate mainly through […] receptors.
dopamine, neuropeptides, prostanoids
G-protein-coupled
Neuromodulators are released by […] and […] , and produce […] pre- or postsynaptic responses.
neurons and by astrocytes
slower
[…] are released mainly by non-neuronal cells and act on tyrosine kinase-linked receptors that regulate gene expression and control neuronal growth and phenotypic characteristic.
Neurotrophic factors
Do neurons only release one neurotransmitter?
[…] is the main excitatory NT in the CNS.
[…] and […] are also excitatory but to a lesser extent / in limited areas.
Glutamate
Aspartate / homocystenate
Where does the glutamate used as an NT come from?
- How is glutamate stored in neurons?
- How is it released from neurons?
- How is it uptaken into neurons?
How is glutamate action terminated?
Which glutamate receptor is faster responding - AMPA or NMDA?
AMPA
[…] is the main inhibitory NT in the CNS.
[…] is also an important inhibitory molecule in the spinal cord and brainstem.
GABA
Glycine
Most GABAergic neurons are […] in length and are of the [….] type.
Short
Interneuron
True/false: very few neurons are sensitive to GABA.
False - nearly all neurons are
Describe how GABA is made.
GABA is formed from glutamate by the action of glutamic acid decarboxylase (GAD), an enzyme found only in GABA-synthesizing neurons in the brain.
- GABAergic […] take up GABA via specific transporters, thus removing GABA after it has been released.
- GABA can be destroyed by a […] reaction in which the amino group is transferred to yield glutamate. This reaction is catalyzed by […], an enzyme located primarily in astrocytes.
- neurons and astrocytes
- transamination; GABA transaminase
How is glycine made as a NT?
How do benzodiazepines enhance the action of GABAergic neurons?
Make Cl- channels stay open longer or make them cycle between open/closed more quickly
- How is Ach synthesized?
- How is choline taken up into neurons?
- How is Ach loaded into vesicles?
How is the action of Ach terminated?
ACh acts on both nicotinic […] and muscarinic […] receptors in the CNS
ionotropic
metabotropic
Where is most norepinephrine produced in the CNS?
Pons and medulla (locus coereleus)
Where is all epinephrine produced in the CNS?
Medulla
What other organ makes NE and E?
Adrenal medulla
How are epinephrine and norepinephrine made?
What are the receptors for norepinephrine, dopamine and serotonin?
What are 3 reasons why reuptake of unused neurotransmitter is important?
What are the 2 enzymes that metabolize catacholamines?
All catecholamine receptors belong to the […] family
G-protein-coupled receptors (metabotropic)
- What is a diffuse modulatory system?
- What neurotransmitters are utilized by these systems?
- Diffuse modulatory systems have powerful effects on very large numbers of neurons in widespread regions of the brain
- Ach, NE, Serotonin, Dopamine
What are the major classes of neurotransmitter systems?
- Monoamines
- Acetylcholine
- Glutamate
- GABA
- Peptides
- Endocannabinoids
- Gaseous transmitters
What are the 2 subclasses of monoamines?
Catecholamines (dopamine, norepinephrine, epinephrine)
Indolamines (serotonin, melatonin, histamine)
Norepinephrine is made in the […] and projects to […]
Locus coeruleus
Spinal cord, cerebellum, many higher cortical structures
Serotonin is made in the […] and projects to the […]
Raphe nucleus
Spinal cord, cerebellum, higher cortical areas
Dopamine is made in the […] , […] and the […] and projects to the […]
Ventral tegmental area –> projects to frontal cortex and limbic structures
Substantia nigra –> projects to basal ganglia
Arcuate nucleus in the hypothalamus –> anterior pituitary (prevents prolactin release)
Acetylcholine is made in the […], […], and […] and projections from these structures go to the […]
Septal nuclei –> projects to higher subcortical structures
Nucleus basalis –> projects to higher cortical structures
PMECT complex –> projects to brainstem, basal ganglia
Dopamine that is synthesized in the substantia nigra terminates release on the striatum of the basal ganglia. What effect does dopamine have on the striatum?
Motor control
Dopamine that is synthesized in the ventral tegmental areas terminates release on the nucleus accumbens (hypothalamus), amygdala, hippocampus, and prefrontal cortex . What effect does dopamine have on these structures?
Memory
Motivation
Reward and desire
Addiction
Dopamine that is synthesized in the arcuate nucleus of the hypothalamus terminates its release on the anterior pituitary gland. What is the function of dopamine in this pathway?
Hormonal regulation
Maternal behavior
Pregnancy
Describe the synthesis of dopamine and norepinephrine.
Tyrosine – [tyrosine hydroxylase] –> L-DOPA – [DOPA decarboxylase] –> Dopamine – [DOPA hydroxylase] –> norepinephrine
What are the fates of dopamine after it has been made from tyrosine?
- In a neuron that is noradrenergic, it can be made into norepinephrine
- In a neuron that is dopaminergic, it can be loaded into vesicles by VMAT2 (vesicular transporter protein) and then released into the synaptic cleft following influx of Ca2+ from an AP.
- Once in the cleft it can bind to dopamine receptors on the post-synaptic neuron (D1 or D2) to transduce the signal to that neuron or it can bind to a D2 receptor on the pre-synaptic neuron to inhibit the presynaptic neuron, or enter back into the presynaptic neuron through a reuptake transporter.
- Additionally, it can diffuse out of the clef, be degraded by an enzyme or uptaken by an astrocyte.
What 2 enzymes are responsible for degrading dopamine and other monoamines?
Monoamine oxidase (MAO)
Catechol-o-methyltransferse (COMPT)
Where is MAO found?
Where is COMPT found?
Mitochondria of presynaptic neuron and liver
Postsynaptic neuron, astrocytes, liver
Explain what is happening in this image?
Dopamine is made, loaded into vesicles and sent to synapse.
If it diffuses into blood stream, can be picked up in liver and broken down by MAO and COMPT.
If it re-enters the presynaptic neuron it can be loaded into vesicles or broken down by MAO in the mitochondria.
If it enters the postsynaptic neuron it an be broken down by COMPT.
D1 like dopamine receptors are […] type of receptors whereas D2 like dopamine receptors are […] type of receptors
Gs
Gi
What is the effect of drugs like amphetamines and adderall on neurons that release monoamines?
These drugs are similar enough in structure to monoamines that they can enter the presynaptic neuron through monoamine transporters. Once inside the neuron, they try to enter the vesicles that contain the monoamines but the vesicles are already full so some of the monoamines are forced out into the cytosol of the neuron. The increased [monoamines] in the cytosol forces some of the monoamines to diffuse across the membrane into the synapse independent of action potential firing. This can lead to activty in the postsynaptic neuron without presynaptic neural signaling to do so.
What is the effect of drugs like cocaine and ritalin on neurons that release monoamines?
Cocaine and ritalin are similar enough to monoamines that they are able to interact with the reuptake transporter but are too large to actually be transported through. As such, they block the transporter, so any monamine that is released as a result of the firing of an action potential will be unable to re-enter the presynaptic neuron and will accumulate in the synapse leading to increased stimulation of the postsynaptic neuron.
How is caffeine a stimulant?
It is an antagonist of adenosine, which is involved in decreasing our alertness / consciousness
How is serotonin made?
Tryptophan – [tryptophan hyroxylase] –> 5-HTP – [5HTP decarboxylase] –> 5HT (serotonin)
Describe the fate of serotonin after it has been made in the presynaptic neuron.
Very similar to dopamine. Vesicle –> synapse –> bind receptor on post synaptic neuron
OR
bind autoreceptor and inhibit presynaptic neuron
OR
re-enter presynaptic neuron via Serotonin reputake transporter (SERT) where it can then be repacked into vesicle or degraded by MAO in mitochondrial membrane
OR
diffuse out of cleft
OR
be degraded by enzyme (MAO or COMPT)
Histamine is produced in the […] and proejcts to the […]
Tuberomamillary nucleus
spinal cord, cerebellum, frontal cortex, somatosensory cortex, limbic system
How is histamine synthesized?
What are the effects of histamine on the:
- Stomach
- Brain
- Immune system
From histidine
- increase acid production
- regulate sleep, hormonal secretion, memory, arousal
- vasodilator in allergic / immune response
How is histamine broken down?
Taken up into astrocyte and broken down by histamine methyltransferase.
For histamine, H1 and H2 receptors are […] while H3 receptors are […]
Excitatory
Inhibitory (inhibit release of other neurotransmitters from nearby axons)
Unlike the other monoamines, histidine cannot do what process after it is released into the synapse?
It cannot be reuptaken by the presynaptic neuron, but all the other fates are the same as other monoamines
True or false: there are very few neuropeptides in the CNS.
False - there are hundreds
True or false: all neuropeptides belong to one family of molecules.
False - there are many families
True or false: neuropeptides all have their own genes
False - a single gene can give rise to several neuropeptides
Neuropeptides are processed and stored in […] core vesicles which are assembled in the […] and transported to the […]
Large, dense
Golgi apparatus
Synapse
How does synthesis of neuropeptides differ from that of other neurotransmitters (like dopamine, NE, serotonin, etc.)?
True or false: neuropeptides tend to be released with other small molecule neurotransmitters (like glutamate, GABA, serotonin, etc.).
True - they help modulate the effect of the neurotransmitter
How is the action of neuropeptides terminated?
Peptidases cleave peptide bonds to release individual AAs
What enzyme makes NO?
Neuronal nitric oxide synthase (nNOS)
When is NO made?
Production is increased by mechanisms that increase intracellular Ca2+
What is the effect of NO on tissues?
Increases cGMP producing both inhibitory and excitatory effects
Vasodilation –> bring in more blood
Explain the signaling cascade that results in production of NO and its action on target tissue.
Ligand binds to receptor –> leads to increased concentration of intracellular Ca2+ –> Ca2+ interacts with calmodulin to form Ca2+ - calmodulin complex –> complex activates NOS –> NOS converts arginine to citruline + NO –> NO diffuses out of neuron and into nearby endothelial cell where it activates gyanylyl cyclase to produce increased cGMP which causes vasodilation
How are endocannabinoids synthesized?
On demand from lipid membrane precursors
Endocannabinoids act as […] neurotransmitters, moving from […] neuron to […] neuron.
Retrograde
Postsynaptic
Presynaptic
What is the function of endocannabinoids?
Fine tune response of presynaptic neuron –> boost or dampen response
How are endocannabinoids broken down?
by fatty acid amide hydrolase (FAAH) in the inner membrane of mitochondria
Describe the distribution of CB receptors in the brain.
Why are there so many?
So many because they modulate interactions of so many other neuronal connections
Describe how sildenafil (viagra) works.
cGMP that is produced as a result of NO release into endothelial cells is typically broken down by PDE 5. Sildenafil inhibits PDE5, allowing cGMP to exert its effects longer leading to prolonged vasodilation.
