Neurotransmitters Flashcards
(90 cards)
1
Q
Classically, what are neurotransmitters?
A
substances that:
- are stored in vesicles in the presynaptic ending
- are released upon nerve activity
- diffuse to the post synaptic cell and combine with sepcific receptors
- produce a change in conductance in the postsynaptic cell
- are inactivated by hydrolysis, uptake or diffusion
2
Q
How are gaseous transmitters (No and CO) different than classical neurotransmitters?
A
They are:
- not stored in vesicles
- released as soon as synthesized
- do not combine with surface receptors on a postsynaptic cell but rather interact directly with the second messegner system inside
- Inactivate by diffusion away from the target
3
Q
What are examples of classic neurotransmitters?
A
A. Acetylcholine
B. Biogenic amines
C. Amino acid transmitters
4
Q
What’s another name for classic neurotransmitters?
A
small-molecule transmitters
5
Q
Describe acetylcholine as a neurotransmitter. What disease it is known to be involved with?
A
Acetylcholine is a primary transmitter of the peripheral nervous system.and is also involved in several CNS pathways.
Degeneration of certain cholinergic paths occur in Alzheimer’s disease
6
Q
What are examples of some biogenic amines?
A
Catecholamines (dopamine, norepinephrine, epinephrine), seratonin, and histamine
7
Q
What are catecholamines synthesized from?
A
the amino acid tyrosine
8
Q
What are three examples of catecholamines?
A
- dopamine (DA)
- norepinephrine (NE)
- epinephrine (E)
9
Q
Where is dopamine generally found?
A
primarily in midbrain and diencephalon
10
Q
What disease degenerates dopamine (DA) pathways?
A
Parkinson’s
11
Q
What group of disorders are linked to dopamine (DA) systems?
A
schizophrenia
12
Q
Where is norepinephrine primarily found?
A
- In post ganglionic sympathetics
2. from the locus coeruleus in the brain stem to the forebrain
13
Q
What does noepinephrine influence?
A
sleep, wakefulness, attention, and feeding
14
Q
What is epinephrine’s role?
A
As a hormone in stress response and a neurotransmitter in the brain of unknown function
15
Q
what is serotonin synthesized from?
A
tryptophan
16
Q
Where is serotonin found?
A
in wide spread projections from the raphe nuclei in the brain stem to brain and cerebellum
17
Q
What is serotonin implicated with?
A
the onset of sleep, mood emotional behavior, and certain psychotic disorders
18
Q
What is histamine synthesized from?
A
histidine
19
Q
where is histamine present?
A
in mast cells (non-neuronal cells) and in the neurons of the hypothalamus (which project to almost all brain and spinal cord)
20
Q
What does histamine mediate?
A
arousal
21
Q
Name four amino acid transmitters
A
- glycine (gly)
- gamma-aminobutyric acid (GABA)\
- glutamate (glu)
- aspartate (asp)
22
Q
Which of the amino acid transmitters are inhibitory?
A
glycine and gamma-aminobutyric acid (GABA)
23
Q
Which of the amino acid transmitters are excitatory?
A
glutamate and aspartate
24
Q
Where is glycine found?
A
in the spinal cord and brain stem
25
where is gamma-aminobutyric acid (GABA) found?
in the CNS
26
What is GABA deficit implicated with?
Huntington's chorea (abnormal involuntary movements)
27
What is the most prevalent excitatory transmitter in the brain?
GLUTAMATE
28
What results from excess glutamate in the CNS?
cell death from acting as an excitotoxin
29
True or false: Aspartate is a nearly ubiquitous inhibitory transmitter.
False; aspartate is nearly ubiquitous excitatory transmitter
30
What are neuropeptides? How are they synthesized? What's their function?
polypeptides synthesized de novo in the soma, packaged in vesicles and transported via axoplasmic transport to axon terminals or sites of released.
Synthesized as pre-propeptides and are cleaved to form the appropriate final product in the vesicles.
They function neurotransmitters, neuromodulators and hormones
31
Where are neurotransmitters released? What do they do? How are they terminated?
released from presynaptic neuron.
Produce a conductance change in the postsynaptic cell
Terminated by diffusion and also peptidases
32
What are some properties of neuromodulators?
They do not necessarily produce a conductance change in the target cell but do alter some aspect of cell function (e.g. ecitability, amount of trnsmitter released, even products synthesized by the cells.
They modulatory effects that can be slow in onset and slow to dissipoate (hours to days)
33
Do all neuromodulators acivate G-protein couple receptors?
Yes
34
What is an example of a neuromodulator stimulating an intracellular signal cascade via activating a G-protein coupled receptor?
activation of adenylyl cyclase and elevation of c-AMP
35
What are classes of neuropeptides? What can they also act as?
1. opoids
2. gut-brain and hypophysiotrophic
Many peptides can also act as neuromodulators or transmitters
36
What are three types of opoids?
1. endorphin
2. enkephalin
3. dynorphin
37
where is endorphin derived from and what does it bind preferentially to?
derived from propionmelanocortin and binds preferentially to mu-receptors
38
where is enkephalin derived from and what does it bind preferentially to?
enkephalin are derived from proenkephalin and bind preferentially to delta receptors.
39
where is dynorphin derived from and what does it bind preferentially to?
derived from prodynorphin and binds preferentially to K receptors.
40
What is coexistance (in terms of neurotransmitters)?
when many neuropeptides and classical neurotransmiters are found in the same nerve terminals. Often Neuropeptides act as neuromodulators in these instances
41
What are three types of gaseous transmitters/modulators?
```
Nitric oxide (NO)
Carbon Monoxide (CO)
Hydrogen Sulfide [sometimes]
```
42
What was NO first identified as in blood vessels?
endothelial-derived relaxing factor
43
What is Nitric oxide synthesized from?
L-arginine by NO synthase
44
IS nitric oxide stored in synaptic vessels?
no!; it is diffused from presynaptic terminal after synthesis
45
What does NO directly react with?
a second messenger system via diffusion (NOT receptors on the post synaptic cell)
46
What is an example of a second messenger system that NO interacts with?
activation of guanylyl cyclase to increas cGMP
47
What is carbon monoxide synthesized from?
synthesized from heme by heme oxygenase
48
Is carbon monoxide placed into vesicles or does it diffuse through cell membranes when synthesized?
diffuse through the cell membrane
49
What is one major action of carbon monoxide?
activation of guanylyl cyclase
50
Which gas(es) activates guanylyl cyclase? What is the result?
Nitric oxide and Carbon monoxide
Results: increase cGMP
51
What are the two types of Neurotransmitter receptor mechanisms?
1. Directly gated ion channels
| 2. Indirectly gated ion channels
52
What are other names for a directly gated ion channels?
ligand-gated and ionotropic receptors
53
What does it mean to be a directly gated ion channel?
the transmitter receptor is part of the ion channel (i.e. a single macromolecule forms both the recognition site and the on channel). Therefore, binding of a neurotransmitter produces a conformation change in the macromolecule that results in opening of the channel
54
What are four types of ligand-gated, ionotropic receptors, or directly gated ion channels?
1. nicotinic ACh receptor
2. NMDA glutamate receptor
3. GABA_A receptor
4. glycine receptor
55
What is the mechanism of the nicotinic ACh receptor?
binding of two ACh molecules initiates conformational change, which allows flux of Na+ into and K+ out of the cell, resulting in depolarization
56
What is the mechanism of NMDA glutamate receptors? What does it result in?
First, the ion channel is plugged by Mg2+ at resting potential and does not conduct well when activated by glutamate unless the membrane is sufficiently depolarized (20-30mV) to drive Mg2+ out of the channel.
Once unplugged, the channel is fully opened by glutamate for high permeability to Ca2+, as well as Na+ and K+
57
True or false: Cells which contain NMDA receptors usually have only NMDA receptors, and cells which contain non-NMDA receptors only have non-NMDA receptors.
False; cells with NMDA receptors usually have non-NMDA glutamate reeptors also.
58
What is the effect of non-NMDA receptors?
activation of non-NMDA receptors depolarizes the cell
59
What happens as non-NMDA receptors increase? What is the effect on NMDA channels and the cell?
as depolarization through non-NMDA receptors increase, NMDA channels are unplugged and the current through these channels increase (for Ca2+, Na+ and K+)
60
What is the result of Ca2+ influx through NMDA channels?
- activation of Ca-dependent second messenger systems
| - possibly cell death (if too much Ca2+ enters)
61
Name one example of a Ca-dependent second messenger system
Ca-Calmodulin/kinase
62
What is important about the GABA_A receptor?
it is responsible for most of the inhibition in the CNS
63
What happens when GABA binds to GABA_A?
it opens a Cl-selective channel
64
Describe the GABA_A receptor
the receptor has GABA binding sites, as well as separate sites that bind other substances which may modify the GABA_receptor channel activity while having little effect by themselves
65
What other substances bind to GABA_A?
1. benzodiazephines (e.g. Valium)
2. barbiturates (e.g. Phenobarbital)
3. steroids (e.g. metabolites of steroid hormones)
4. ethanol
66
what is the effect of benzodiazepines on the GABA_A receptor channels?
increasing Cl- current by increasing the frequency of channel opening produced by GABA
67
What is an example of a benzodiazepines?
Valium
68
What is the effect of barbituarates on the GABA_A receptor?
increase of Cl-current by increasing the DURATION of channel opening produced by GABA
69
What is an example of a barbiturate?
Phenobarbital
70
What are the effects of steroids on the GABA_A receptor?
increase Cl- current by increasing the duration of channel opening produced by GABA
71
What other substance has similar effects as steroids on the GABA_A receptor?
barbiturates
72
What is the effect of ethanol on the GABA_A receptor?
increases GABA-induced Cl- currents
73
Besides substances, what else modulates the GABA_receptor? What are their effects?
second-messenger pathways alter inhibitory activity in the CNS
74
What is an example of a second-messenger pathway modulating GABA_A receptors?
phosphorylation by either protein kinase C (PKC) or protein kinase A (PKA) reduces Cl- current
75
What two receptors mediate inhibition in the CNS?
GABA_A receptors and glycine receptors
76
What type of channel is a glycine receptor?
A directly gated ion channel (i.e. a ligand gated or ionotropic receptor)
77
What is the effect of the glycine receptor?
glycine receptors mediate the rest of the inhibition in the CNS not mediated by GABA. Binding of glycine opens a Cl-selective channel
78
What are the effects of GABA_A receptors and glycine receptors?
both open a selective Cl- channel, thus mediating the inhibition in the CNS
79
What is another name for receptors that gate ion channels indirectly?
metabotropic receptors
80
Describe the form and function of receptors that gate ion channels indirectly (metabotropic receptors)
Metabotropic receptors are linked to G-proteins and make up the largest group of receptors. In this case, the receptor and ion channel are NOT part of the same macromoleucle but are distinct, separate entities linked together by a G-protein
81
What modulates receptors that gat ion channels indirectly?
The g-protein that connects the receptor and the ion channel
82
What are the two general pathways by which G-proteins modulate ion channels?
1. the G-protein directly affects the channel
| 2. the G-protein activates a second messenger system
83
What is the pathway where G-protein directly affects the ion channel known as?
the membrane-delimited pathway
84
What is the mechanism of the the membrane-delimited pathway?
the binding of a neurotransmitter to the receptor activates a G-protein and the beta-gamma subunits of the G-protein diffuse through the membrane to interact with nearby channels.
85
What is an example of a membrane-delimited pathway?
M_2 ACh receptor on the heart which increases K permeability
86
What are general properties of the membrane-delimited pathway?
- fast indirect pathway with latency of 30-100ms
| - localized response because of limited diffusion of G-protein within the membrane
87
Which has a localized response: membrane-delimited pathways or G-protein activated second messenger systems?
membrane-delimited pathways
88
What is the mechanism what occurs when the G-protein activates a second messenger system?
The G-protein (usually alpha subunit) activates an enzyme which gives rise to a second messenger (like Ca2+, cAMP, cGMP, IP_3, DAG, or arachidonic acid). The second messenger then directly modulates the ion channel and activates a inase which phosphorylates a protein (either the channel itself or a regulatory protein which acts on the channel), causing the channel to open or close
89
What is an example of a second messenger system activated by a G-protein?
Beta_1 receptor activation by norepinpehrine in the heart leads to activation of adenylyl cyclase and an in increase in c-AMP, which activates protein kinase A that phosphorylates the L-type Ca channel leading to an increase in Ca influx
90
What are general properties of G-proteins activating a second messenger system?
- slow pathway w/ latency of 100s to 1000s ms
- capable of wide spread effects because of the production of soluble messengers (like cAMP) which can diffuse throughout the cytoplasm
- capable of a great deal of amplification
- can generate very-long lasting changes in cells
