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Molecular Neuroscience I > 1 - Intro > Flashcards

1 - Intro Flashcards

1
Q

How are neurotransmitter vesicles organized in the resting state?

A

Attached to microtubules

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2
Q

What is the five criteria for neurotransmitters?

A
  • Synthesis of the molecule must occur within the neuron for de novo synthesis
  • Storage of the molecule occurs within the nerve ending prior to release
  • Release of the molecule from the presynaptic ending occurs in response to an appropriate stimulus such as action potential
  • There is binding and recognition of the putative neurotransmitter molecule on the postsynaptic target cell
  • Mechanisms exist for the inactivation and termination of the biologic activity of the neurotransmitter
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3
Q

What are neuromodulators?

A

They are released by the nerve endings and have their effect sometimes quite far from the neuron from which they were released. They are not rapidly degraded or taken up, so the amount of time for their activity is not limited as in neurotransmitters. They can either dampen or enhance the excitability of their effector neurons. Examples of neuromodulators are opioid peptides such as enkephalins, endorphins, dynorphins.

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4
Q

True or false? Some molecules can act as a neurotransmitter, neuromodulator and humoral factor.

A

true

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5
Q

What are the five major groups of neurotransmitters?

A
  • Amines
  • Amino acids
  • Purines
  • Gases
  • Peptides
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6
Q

Where are neurotransmitters synthesized in neurons?

A

Non-peptides: Nerve endings, packaged into secretory vesicles

Peptides: Synthesized in cell body and transported down axon

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7
Q

What are the four classifications of neurotransmitter receptors?

A
  • Metabotropic (G-protein coupled)
  • Ionotropic (Ligand gated receptors)
  • Tyrosine kinase receptors
  • Intracellular receptors
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8
Q

Which is the most common classification of neurotransmitter receptor?

A

Metabotropic (G-protein coupled)

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9
Q

What are the four kinds of second messengers that mediate G-protein coupled receptor signals?

A
  • cAMP
  • cGMP
  • IP3
  • Calcium ion
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10
Q

What are the two types of agents that can act on G-protein coupled receptors?

A
  • Agonists (stimulate receptor)

- Antagonist (inhibits receptor - blocker)

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11
Q

What is the structure of G protein-coupled receptors?

A
  • 7 transmembrane domains
  • N terminal is extracellular
  • C terminal is intracellular
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12
Q

Phosphorylation of what components on G protein-coupled receptors can affect G protein-receptor interaction?

A

Hydroxyl groups on serine and threonine residues

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13
Q

The G protein interacts with what part of the G-protein coupled receptor?

A

Third cytoplasmic loop between V and VI transmembrane regions

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14
Q

How is the G protein activated?

A
  • An agonist binds to the receptor and causes the release of GDP from the G protein
  • GTP can then bind (activating the G protein)
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15
Q

How is G protein activity terminated?

A

Hydrolysis of GTP

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16
Q

What protein facilitates the termination of the G protein by hydrolyzing GTP?

A

RGS

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17
Q

β-adrenergic histamine and serotonin are agonists for the receptor of what G protein? What are the associated effectors?

A

Gs

Gs stimulates adenylyl cyclase, which increases cAMP

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18
Q

α2-adrenergic ACh, opiods and serotonin are agonists for the receptor of what G protein? What are the associated effectors?

A

Gi

Gi inhibits adenylyl cyclase, decreasing cAMP

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19
Q

Odorants are agonists for the receptor of what G protein? What are the associated effectors?

A

Golf

Golf increases adenylyl cyclase in olfactory epithelium

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20
Q

The Go G protein is present where?

A

Present in the brain and has receptor presumably activated by neurotransmitters, signalling pathway is unclear.

21
Q

Acetylcholine (M1,3,5) is an agonist for the receptor of what G protein? What are the associated effectors?

A

Gq

Gq stimulates phospholipase C and in consequence increases IP3 (inositol-1,4,5-triphosphate), diacylglycerol and cytoplasmic calcium ion

22
Q

photoreceptors are agonists for the receptor of what G protein? What are the associated effectors?

A

Gt

Gt stimulates cGMP phosphodiesterase and in consequence decreases cGMP in the phototransduction process.

23
Q

How does cAMP (second messenger) activate ion channels and transcription factor modulation?

A

Four cAMP molecules bind to a protein kinase A (PKA) which allows it to phosphorylate ion channels.

Translocation into the nucleus allows modulation of the activity of transcription factors such as the cAMP responsive element binding protein (CREB) or the activation transcription factor (ATF) families, leading to either the induction or the repression of expression of specific genes.

24
Q

How does phospholipase C cause the release of calcium into neurons?

A
  • Gq protein activates phospholipase C (PLC)
  • PLC cleaves PIP2 (phospholipid phosphoatidylinositol-4,5-biphosphate) into DAG (diacylglycerol) and IP3 (inositol triphosphate).
  • DAG remains in the membrane, where it recruits and activates protein kinase C
  • IP3 stimulates the opening of IP3 mediated Ca channels on the endoplasmic reticulum
25
Q

What is vibrio cholerae?

A

A bacteria that produces a G protein-coupled receptor toxin, which prevents the hydrolysis of Gs bound GTP, which results in permanently activated Gs protein. Resultant increased cAMP concentration in the intestinal epithelial cells activate Cl channels which causes an influx of water and electrolytes into the gut.

26
Q

What is heat-labile enterotoxin?

A

Produced by some strains of E. coli, inactivates Gi proteins which result in activation of cAMP, PLA2 and PLC pathways.

27
Q

What does the toxin produced by Pasteurella multocida do?

A

Activates Gq and Gi proteins which causes numerous pathological conditions (often skin deformations and necrosis) in humans and domestic animals.

28
Q

What are three diseases connected to G proteins?

A
  • Color blindness (defective receptor)
  • McCune-Albright syndrome (missense mutation in the GNAS2 gene encoding Gsα subunit of G protein, resulting in downregulation of cAMP signaling. Deformity of bones, pigment patches, hormone hypersecretion and early puberty result
  • Alzheimers could be a result of abnormal G protein coupled receptors, especially those involved in phosphoinositide hydrolysis
29
Q

What are the two type of channels associated with ionotropic receptors?

A
  • Voltage gated ion channels open under depolarization (potassium channels)
  • Ligand gated ion channels open under allosteric binding to the channel protein, conducts both Ca and Na ions

Some channels have properties of both types (voltage and ligand gated)

30
Q

What are the three ligand-gated channel types?

A
  • Cys-loop ion channel family
  • Ionotropic glutamate receptors
  • ATP-gated purinergic receptor channel family
31
Q

What is the cys-loop ion channel family?

A

pentameric fast ligand gated receptors

Consist of two groups:

  • Cationic channels-serotonin 5-HT3 receptors and nAChRs
  • Anionic (Cl-) channels for GABAa and glycine
32
Q

What are ionotropic glutamate receptors? What are the three subgroups of ionotropic glutamate receptors?

A

Multimeric (4/5 subunits) assemblies of four or five subunits, divided into three subgroups based on their pharmacological/structural similarities:

  • N-Methyl-D-aspartate (NMDA)
  • A-amino-3-hydroxyl-5-methyl-4-isoxaspartate (AMPA)
  • Kainate receptors
33
Q

What is the ATP-gated purinergic receptor channel (P2X) family? How many ATP are required to open one?

A

Non selective cation-permeable channels that open in response to extracellular ATP, at least 3 ATP molecules are required to activate a P2X receptor.

They are multimeric (3 or 4 subunits)

34
Q

What are the major family members of cys-loop receptors? (4)

A
  • nAChRs
  • 5-HT3
  • GABAa
  • Glycine receptors
35
Q

What are the major family members of glutamate receptors? (3)

A
  • NMDA
  • kainate
  • AMPA
36
Q

What is another name for ATP-gated channels and purinergic receptors?

A

P2X receptors

37
Q

What are the antagonists (2) and agonists (2) of nAChRs receptors?

A

Antagonists

  • α-bungarotoxin
  • D-tubocurarin

Agonists

  • ACh
  • Nicotine
38
Q

What are the antagonists (2) and the agonists (1) of 5-HT3 receptors?

A

Antagonists

  • Granisetron
  • Ondansetron

Agonists
- Serotonin

39
Q

What are the antagonists (2) and agonists (5) of GABAa?

A

Antagonists

  • Picrotoxin
  • Bicuculline

Agonists

  • GABA
  • alcohol
  • Barbiturates
  • Steroids
  • Benzodiazepines
40
Q

What are the antagonists (1) and agonists (3) of glycine cys-loop receptors?

A

Antagonist
- Strychnine

Agonists

  • Glycine
  • Taurine
  • β-alanine
41
Q

What are the antagonists (4) and agonists (2) of NMDA receptors?

A

Antagonists

  • APV
  • MK-801
  • Phencyclidine
  • External magnesium ion

Agonists

  • Glutamate
  • NMDA
42
Q

What are the antagonists (1) and agonists (2) of kainate receptors?

A

Antagonist
- CNQX (nitroquinoxaline)

Agonists

  • Glutamate
  • Kainate
43
Q

What are the antagonists (2) and agonists (3) of AMPA receptors?

A

Antagonists

  • CNQX (nitroquinoxaline)
  • Philantothoxin

Agonists

  • Glutamate
  • AMPA
  • Quisqualate
44
Q

What are the antagonists (1) and agonists (2) of P2X receptors?

A

Antagonists
- Over 10 mM of α,β-methylene ATP

Agonists

  • Extracellular ATP
  • Under 10 mM of α,β-methylene ATP
45
Q

What are two diseases related to ligand gates channels?

A
  • Myasthenia gravis (decreased expression of nAChR in the postsynaptic site of neuromuscular junctions from T-lymphocyte dependant autoimmune reaction against nAChRs or hereditary mutation)
  • Juvenile myoclonic epilepsy (missense mutation of GABAa receptor α1 subunit. Accounts for 5-10% of all epilepsy patients)
46
Q

Receptor tyrosine kinases mediate signalling of what?

A

Insulin and some growth factors

47
Q

How do receptor tyrosine kinases communicate with second messengers?

A

Autophosphorylation of tyrosines in the intracellular domain of the receptor

  • The phosphorylated tyrosines function as binding sites for proteins with SH2 (Src homology 2 - tyrosine binding) domains. These proteins are second messengers such as phospholipase C, PI3 and adaptor proteins
48
Q

What is a glucocorticoid receptor?

A

In intracellular receptor

Binds heat shock protein 90 (HSP90), which is released following binding with a ligand. The receptor translocates to the nucleus where it acts as a transcription factor to upregulate anti-inflammatory genes and downregulate pro-inflammatory cytokines

49
Q

What do intracellular receptors require as ligands?

A

Ligands that are membrane permeable

Molecular Neuroscience I (8 decks)

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