CHAPTER 4: NEUROTRANSMITTERS AND NEUROMODULATORS Flashcards
1
Q
What is the excitatory amino acid NT in the brain?
A
glutamate
2
Q
What is the inhibitory amino acid neurotransmitter in the brain?
A
-Gamma-aminobutyric acid or GABA
3
Q
What is the inhibitory amino acid NT in the spinal cord and lower brain stem?
A
glycine
4
Q
What is glutamate?
A
- amino acid
- most important excitatory neurotransmitter in the brain
5
Q
What is a vesicle glutamate transporter?
A
-proteins in the vesicle membrane that pump glutamate into a vesicle
6
Q
How is glutamate produced, stored and released?
A
- PRODUCTION: Synthesized from a precursor (glutamine) by an enzyme (glutaminase).
- STORAGE: vesicle glutamate transporters package glutamate into vesicles.
- RELEASE: action potential, glutamate released from presynaptic terminal.
7
Q
What are the 4 major types of glutamate receptors?
3 ionotropic receptors, 1 metabotropic receptor
A
- ionotropic: NMDA receptor, AMPA receptor, kainate receptor.
- metabotropic: metabotropic glutamate receptor
8
Q
What is the main function of metabotropic glutamate receptors?
A
-presynaptic autoreceptors
9
Q
What is the main function of AMPA and NMDA receptors?
A
-important roles in the cellular basis of learning and memory.
10
Q
How can glutamate open a calcium channel on an NMDA receptor?
A
- a glycine molecule must be attached.
- a magnesium ion must be removed from the magnesium binding site (this happens if the post synaptic membrane is partially depolarized.
11
Q
What are the two conditions for an NMDA receptor to open?
A
- glutamate is present
- postsynaptic membrane is depolarized.
- NMDA receptor= voltage and neurotransmitter dependent ion channel
12
Q
How does PCP (phencyclidine) act on the calcium ion channel?
A
- binds to its site which is located deep within the ion channel, next to the magnesium binding site.
- Prevents the calcium ions from passing through the ion channel.
13
Q
Which other drug has similar effects as PCP?
A
Ketamine, thought to bind on the same site as PCP.
14
Q
How is glutamate reuptaken and deactivated?
A
- Removed from synapse by excitatory amino acid transporters
- Broken down into it’s precursor (glutamine) by the enzyme glutamine synthase
15
Q
What is PCP?
A
-Phencyclidine a drug that binds with the PCP binding site of the NMDA receptor and serves as an indirect antagonist
16
Q
What are excitatory amino acid transporters?
A
proteins that remove glutamate from the synapse
17
Q
What is glutamine synthase?
A
Enzyme that breaks down glutamate into its precursor glutamine.
18
Q
What is GABA?
A
- Amino acid
- Most important inhibitory NT in the brain
19
Q
Where is GABA distributed?
A
widespread distribution throughout brain and spinal cord
20
Q
How is GABA produced?
A
- from a precursor: glutamic acid
- by the action of enzyme GAD
21
Q
What is a vesicle GABA transporter?
A
-Proteins in the vesicle membrane that pump GABA into a vesicle
22
Q
What is the main function of GABA-secreting neurons?
A
-exhibit inhibitory influence to keep brain stable
23
Q
What are seizures are result of?
A
- lacking or poorly functioning GABA-secreting neurons or receptors
- During a seizure interconnected excitatory neurons all fire uncontrollably
24
Q
Are GABAa receptors ionotropic or metabotropic?
A
ionotropic
25
What channels do GABA a receptors control?
-chloride channels
26
How do some drugs produce their effects with GABA receptors?
- barbiturates, alcohol, and benzodiazepines
| - they bind at various GABAa binding sites
27
How is GABA reuptaken and deactivated?
- removed from synapse by GABA transporters
| - broken down by enzyme GABA aminotransferase.
28
What is glycine?
-Inhibitory neurotransmitter in spinal cord and lower portions of the brain
29
What are the effects of tetanus on glycine?
-The bacteria that causes tetanus releases a chemical that prevent the release of glycine (and GABA as well)
30
What would the removal of the inhibitory effects of glycine synapses cause?
-continuous contraction of muscles
31
What is a direct antagonist for glycine receptor?
Strychnine
32
Where does Acetylcholine (ACh) function?
Both in CNS and PNS
33
What is ACh's primary role in the PNS?
Primary NT to control muscle contraction
34
In the CNS, what are the 3 specific location sand pathways where ACh is found?
- Dorsolateral pons
- Basal forebrain or nucleus basalis
- Medial septum
35
What is the function of ACh in dorsolateral pons?
-role in REM sleep
36
What is the function of ACh in the basal forebrain or nucleus basalis?
facilitate learning
37
What is the function of ACh in the medial septum ?
memory formation
38
How is ACh produced?
- synthesized from precursors choline and acetylcoenzyme A,
| - by the enzyme choline acetyltransferase (ChAT)
39
What is choline acetyltransferase (ChAT)?
The enzyme that transfers the acetate ion from acetyl coenzyme A to choline, producing the neurotransmitter acetylcholine.
40
What is vesicle ACh transporter?
Proteins in the vesicle membrane that pump acetylcholine into a vesicle
41
What is Botulinum toxin (Botox) and how does it act on ACh?
- produced by the bacteria: clostridium botulinum
- acetylcholine antagonist
- prevents release of ACh by terminal buttons.
42
What is the ionotropic ACh receptor stimulated by?
nicotine (found in tobacco leaves)
43
What is the metabotropic ACh receptor stimulated by ?
muscarine (found in the mushroom amanita muscaria)
44
Which type of ACh receptor is mostly contained in the PNS and why?
- ionotropic nicotinic receptors
| - because muscle fiber shave to contract quickly , and nicotinic receptors are rapid-acting
45
Which type of ACh receptor is mostly contained in the CNS and why?
- metabotropic muscarinic receptors
| - they control ion channels and production of second messengers so they are slower
46
What is ACh deactivated by ?
enzyme acetylcholinesterase (AChE) which is present in the post synaptic membrane.
47
What are AChe inhibitors used for?
to treat myasthenia gravis.
48
What are monoamine NT produced by?
Several regions of the brain
49
What is the general function of monoamine NT?
Modulate functions of widespread regions of the brain either increasing or decreasing brain functions
50
What are the four types of monoamine? ( also included as indolamines)
- dopamine
- norepinephrine
- epinephrine
- serotonin
51
What are the 3 that belong to the subclass of monoamines called catecholamines?
- dopamine
- norepinephrine
- epinephrine
52
What types of post synaptic potentials does dopamine (DA) produce? (excitatory or inhibitory)
both excitatory and inhibitory
53
What functions of the body does dopamine affect?
- movement
- attention
- learning
- reinforcing effect of drugs
54
Where do the three most important dopamine pathways originate?
in midbrain structures: subtantia nigra and ventral tegmental area
55
What is the
-origin
-location of terminal buttons
of the nigrostriatal system?
- ORIGIN: substantia nigra
| - TERMINAL BUTTONS: neostriatum (caudate nucleus and putamen)
56
What is the
-origin
-location of terminal buttons
of the mesolimbic system?
- ORIGIN: ventral tegmental area
| - TERMINAL BUTTONS: nucleus accumbens, amygdala and hippocampus
57
What is the
-origin
-location of terminal buttons
of the mesocortical system?
- ORIGIN: ventral tegmental area
| - TERMINAL BUTTONS: prefrontal cortex
58
What are the behavioural effects of the nigrostriatal system?
control of movement
59
What are the behavioural effects of the mesolimbic system?
Reinforcement effects of addictive drugs
60
What are the behavioural effects of the mesocortical system?
short-term memory, planning, strategies for problem solving
61
What does the degeneration of dopaminergic neurons that connect the substantia nigra with the caudate nucleus cause?
Parkinson's disease
62
What is the precursor for the two major catecholamines (dopamine and norepinephrine)?
tyrosine, which is an essential amino acid that we must obtain from our diet.
63
How is tyrosine modified to become dopamine?
- modified by enzyme tyrosine hydroxylase do become L-DOPA
| - L-DOPA modified by enzyme decarboxylase to become dopamine
64
How does dopamine become norepinephrine?
-converted by enzyme dopamine B-hydroxylase.
65
What are vesicle monoamine transporters?
Proteins in the vesicle membrane that pump monoamine NT into a vesicle.
66
What drug are people with Parkinson's disease often given?
- L-DOPA
| - because it can cross the blood-brain barrier for conversion to DA
67
What are the metabotropic types of dopamine receptors?
-D1, D2, D3, D4, D5.
68
How is DA reuptaken and deactivated?
| diagram
- DA transporters remove DA from synapse
| - Deactivation of catecholamines is regulated by an enzyme called monoamine oxidase (MAO)
69
What drugs serve as agonists for DA?
- amphetamine, methamphetamine (for dopamine and norepinephrine)
- cocaine, methylphenidate (Ritalin). only dopamine
70
What is cocaine used for?
-topical anesthetia
71
What is methylphenidate used for?
enhance attention and impulse control in ADHD
72
Where is NE found?
both CNS and PNS
73
What is epinephrine a synonym of ?
adrenaline
74
What regions of the brain receive input from noradrenergic neurons?
almost every region
75
Where are the cell bodies of the most important noradrenergic system located?
in the locus coeruleus (nucleus located in the dorsal pons)
76
What are the primary effects of an activation of NE neurons?
increase of vigilance and attentiveness.
77
How is NE produced, stored and released?
- As seen earlier, it is transformed from DA so same thing:
- synthesized from DA by enzyme dopamine B-hydroxylase
- since dopamine is already in vesicle, the storage of NE happens in vesicles themselves.
- Released through axonal varicosities.
78
What is an axonal varicosity?
An enlarged region along the length of an axon that contains synaptic vesicles and releases a NT and neuromodulator.
79
How many types of adrenergic receptors are sensitive to both NE and epinephrine and where are they found?
- Four types called alpha a and 2 and beta 1 and 2
- All metabotropic
- Found in neurons in the CNS and various organs of body.
80
How is NE reuptaken and deactivated?
- NE transporter removes excess NE from the synapse
| - Excess NE in the terminal buttons is deactivated by MAO type A.
81
What are MAO inhibiting drugs (MAOIs) sometimes used for?
- to treat depression, but have side effects
| - newer drugs such as selective serotonin, Ne and DA reuptake inhibitors have replaced them.
82
What does serotonin (5-HT) play a role in?
- regulation of mood
- control of eating
- sleep
- arousal
- pain regulation
- dreaming
83
Where is 5-HT found?
- found in 9 clusters
- most is located in the raphe nuclei of the midbrain, pons and medulla
- 2 most important clusters: dorsal and median raphe nuclei
84
What is 5-HT released from
from varicosities, like NE
85
What is the precursor for serotonin?
-the amino acid tryptophan.
85
What is the precursor for serotonin?
-the amino acid tryptophan.
86
What do 5-HT receptors serve as?
- some types of receptors serves as autoreceptors
| - other types serve as postsynaptic receptors
87
How is 5-HT reuptaken ?
serotonin transporter removes it from the synapse
88
What drugs that inhibit the reuptake of serotonin play an important role in treatment of mental illness?
- Fluoxetine (Prozac): treatment of depression, anxiety, OCD.
- MDMA (ecstasy): excitatory and hallucinogenic effects
89
Where is histamine found?
In the tuberomammillary nucleus, locate din the posterior hypothalamus
90
What is the important role of histamine?
wakefulness
91
What is the effect of drugs that block histamines ?
drowsiness
92
How is histamine produced?
-Produced from the amino acid precursor histidine by the action of the enzyme histidine decarboxylase
93
What are the histamine receptors and where are they contained?
- H1, H2, H3, H4
| - contained in CNS
94
What drugs are antagonist to histamine receptors?
-antihistamines like diphenhydramine
95
What are peptides?
-two or more amino acids linked together by peptide bonds
96
How are peptides produced?
-from precursor molecules which are large polypeptides broken into smaller neurotransmitter molecules by special enzymes
97
Where are peptides released from?
- all parts of terminal button
| - no reuptake or recycling
98
What is one of the best known family of peptides?
-endogenous opioid: class of peptides secreted by the brain that act as opiates.
99
How do opioids reduce pain?
-They mimic some of the effects of endogenous opioid and bind to peptide receptors.
100
When were the receptors for opiate drugs discovered?
In the 70s
101
What are the natural ligands for receptors called?
enkephalins
102
What are the three different types of opioid receptors?
mu, delta, kappa.
103
What are the three neural systems that are activated when opioid receptors are stimulated?
- analgesia
- inhibition of defensive responses such as fleeing or hiding
- reinforcement (reward): can lead to abuse
104
What can substances derived from lipids do?
transmit messages within or between cells.
105
How do lipid NT produce, store and release?
- appear to be synthesized on demand, produced or released as needed.
- they are not stored in synaptic vesicles.
106
What are the best known lipid NT?
-endocannabinoids: responsible for the effects of THC
107
What are the two types of cannabinoid receptors?
-CB1 and CB2.
108
What did scientist Agarwal find about THC?
- THC exerts analgesic effects by stimulating CB1
| - acetaminophen also acts on these receptors.
109
How are lipids reuptaken and deactivated?
- anandamide deactivated by the enzyme FAAH
| - anandamide transporters are responsible for the reuptake of anandamide to the presynaptic cell
110
What are nucleosides?
compound that consists of a sugar molecule bound with a purine or pyrimidine base.
111
What are examples of nucleosides?
adenosine and caffeine
