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Molecular Neuroscience I > 4 - Neuropeptides, NO, hydrogen sulfide and Purines > Flashcards

4 - Neuropeptides, NO, hydrogen sulfide and Purines Flashcards

Nitrous oxide Hydrogen sulfide Purines

1
Q

Neuropeptides are packaged into?

A

Neuropeptides are packaged into dense core vesicles (labelled by SEM observations).

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2
Q

Once neuropeptides are packaged into golgi network vesicles, what happens to the vesicles as they are processed?

A

The vesicles are originally large in diameter, but they are concentrated as they are processed, leading to dense core vesicles.

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3
Q

Corticotropin-releasing hormone (CRH) receptors?

A

CRH1 and CRH2 expressed in all brain structures. Regulate variety of functions and involved in anxiety, depression and stress.

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4
Q

Which neuropeptide receptor most involved in pain?

A

Neurotrophin receptors

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5
Q

What do opioid receptors mostly modulate?

A

Pain mediation

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6
Q

The brain has mostly what type of adenosine receptor?

A

A1 and A2A

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7
Q

What is caffeine’s effect on the brain? (which receptors?)

A

Blocks adenosine purinergic receptors in the brain.

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8
Q

What is a neuropeptide?

A

A group of around 100 small peptides involved in neuronal signaling. Synthesized in ribosomes in the form of preprohormones, which are larger precursors that need to be cleaved.

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9
Q

True or false? Neuropeptides often coexist with classical NTs in neurons

A

True

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10
Q

True or false? Neuropeptides mostly act via ionotropic receptors.

A

False. Mostly with metabotropic receptors.

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11
Q

What does substance P do?

A

Induce intestinal contractions. First neuropeptide discovered

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12
Q

What polypeptide is the precursor of many neuropeptides?

A

Proopiomelanocortin (POMC)

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13
Q

What type of enzyme cleaves proopiomelanocortin (POMC) neuropeptide precursors? At what residues?

A

Prohormone cleavases

At lysine and/or arginine residues

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14
Q

What are the three possible melanocortin products from proopiomelanocortin cleavage?

A
  • adrenocorticotrophin (ACTH)
  • melanotrophins (MSH)
  • β-endorphins
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15
Q

What are large granular vesicles (LGVs)?

A

The vesicles that neuropeptides are loaded into (also called large dense core vesicles)

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16
Q

How are neuropeptides packaged?

A
  • Trans golgi network to immature large granular vesicles

- Large granular vesicles fuse to form mature LGVs

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17
Q

True or false?

A

Large granular vesicles can contain a mixture of neuropeptides

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18
Q

True or false? Neuropeptides co-store and co-released can exert opposing actions.

A

True, an example is dynorphin and hypocretin

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19
Q

What are tachykinin receptors?

A
  • Bind endogenous tachykinins (substance P, neurokinin A, neurokinin)
  • Involved in mediation of pain
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20
Q

What are angiotensin II receptors?

A
  • Stimulates Gq protein
  • Stimulates ACTH and vasopressin secretion in the pituitary
  • Increases thirst and desire for salt
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21
Q

What are VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide) transmitters and their receptors?

A

VIP: VPAC1 and VPAC2 receptors

PACAP: PAC1 receptor

Show neuroprotective functions in the CNS

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22
Q

What is NPY1-5R receptor?

A

Stimulated by NPY, which is co-stored and co-released together with ATP and norepinephrine in most sympathetic axon terminals. Coupled to Gi, involved in control of circadian rhythms, anxiety and appetite.

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23
Q

What is somatostatin?

A

A neuropeptide that is widely distributed in the nervous system, and five different G-protein coupled somatostatin receptors have been cloned. Inhibits release of GH in anterior pituitary.

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24
Q

What happens when bombesin receptors are activated?

A
  • Decrease feeding
  • Involved in anxiety,
  • Cancer
  • Circadian rhythms
25
Q

What are bradykinin receptors?

A

Involved in the mediation of pain, hyperalgesia and decrease in blood pressure

26
Q

What are corticotropin-releasing hormone receptors involved in?

A
  • Anxiety
  • Depression
  • Stress
27
Q

What are galanin receptors involved in?

A

Inhibitory effect on NT release and neuroprotective properties. Stimulates neurogenesis.

28
Q

What does a Gal1 (galanin) knockout show?

A

Increased anxiety

29
Q

What does activation of brain ghrelin receptor (GHSR) cause?

A

stimulation of appetite

30
Q

What happens to neurotensin receptors in schizophrenic patients?

A

Lowered receptor density

31
Q

What are neurotrophin peptide receptors associated with?

A
  • Pain
  • Hyperalgesia
  • Neurodegeneration
  • Depression
  • Schizophrenia
32
Q

What are orexin receptors associated with?

A
  • Sleep regulation

- Obesity

33
Q

What do opioid receptors mediate?

A

Pain

34
Q

How is nitric oxide synthesized?

A

Synthesized from L-arginine by nitric oxid synthase (NOS) in the presence of oxygen and cofactors

35
Q

What are the three isoforms of NOS?

A
  • Neuronal NO synthase
  • Immunological or inducible NOS
  • Endothelial NOS
36
Q

What neuropeptide was initially found as epithelium-derived relaxing factor (EDRF)?

A

Nitric Oxide (NO)

37
Q

What process of NO synthesis is calmodulin (CaM) dependent?

A

Synthases binding together into dimers in the oxygenase domain to make a single functional unit (homodimer).

38
Q

How does NO regulate vascular smooth muscles?

A
  • Action potential stimulates neuronal NOS to produce NO
  • NO diffuses to the muscle, activating muscle soluble guanylyl cyclase
  • Guanylyl cyclase converts GTP into cGMP
  • cGMP acts on cGMP dependent protein kinases, phosphodiesterases and cyclic nucleotide-gated ion channels, which results in muscle relaxation
39
Q

Where does nitric oxide synthase show high expression?

A
  • Striatum
  • Olfactory bulb
  • cerebellum
  • Substantia nigra
  • Hippocampus
40
Q

What six behaviours does NO in the brain modulate?

A
  • Learning
  • Feeding
  • Sleeping
  • Reproductive behaviour
  • Aggression
  • Anxiety
41
Q

What neuropeptide has been involved in long term potentiation (LTP) in the hippocampus, cerebral cortex, cerebellum, amygdala and spinal cord and LTD in the cerebellum and striatum?

A

Nitric oxide with it’s cGMP pathway

42
Q

What does NO mediate in peripheral organs?

A

Smooth muscle relaxation

43
Q

NO reacts with superoxide ions to form peroxynitrite in the brain. What is the consequence of this?

A

Peroxynitrite can react with proteins, lipids or DNA and break down to yield the noxious hydroxyl and nitrogen dioxide radicals, NO can also inhibit mitochondrial respiration

44
Q

Inhalation of what neuropeptide can prevent brain injury in premature newborns?

A

Nitric oxide

45
Q

How is nitric oxide used to treat erectile dysfunction?

A

Inhibiting phosphodiesterase 5 (PDE5) will promote cGMP degradation (decrease ability of NO to relax smooth muscle)

46
Q

True or false? Hydrogen sulfide (H2S) is a gas

A

True

47
Q

Where is H2S produced in a cell?

A

Mitochondria

48
Q

What are the actions of H2S?

A
  • cytoprotective (prevents apoptosis)
  • Dilates blood vessels
  • Reduces phosphorylation and ATP biosynthesis
  • Reduces oxidative stress in mitochondria and induce a suspended-animation like state (useful in hypoxia nd preservation of transplantable organs)
49
Q

What are the three transmitters of the purinergic signalling system?

A
  • ATP
  • ADP
  • Adenosine
50
Q

What are the three purinergic receptors?

A
  • PTX receptors (ionotropic)
  • PTY receptors (G protein coupled for ATP and ADP)
  • P1 metabotropic adenosine receptors
51
Q

What are the four adenosine receptors (P1) and where are they found?

A

A1 (CNS, heart)
A2a (Brain, heart, lungs)
A2b (large intestine, bladder)
A3 (lung, liver, brain)

52
Q

True or false? Purinergic receptors are only expressed by neurons?

A

False, also expressed in glia

53
Q

What are purinergic sympathetic co-transmissions?

A
  • When ATP and norepinephrine are co-released from small granular vesicles (SGV)
  • Gast contraction is mediated by ATP, which evokes excitatory junction potentials with the ionotropic P2X
  • Norepinephrine induces slow contraction via activation of α1 metabotropic receptors
  • Neuropeptide Y is released from large granular vesicles to presynaptically inhibit ATP/norepinephrine release
54
Q

How does ATP derived adenosine (ADO) induce vasodilation?

A

It acts on muscular P1 receptors and also via presynaptic receptors located on the perivascular nerves

55
Q

Explain purinergic mechanosensory transduction

A

Distension (stretching membranes) induces release of ATP from epithelium which acts on P2X sensory nerves and the signal is then sent to the CNS

56
Q

What do PTY platelet receptor antagonists do?

A

Inhibiting blood clots in artery diseases

57
Q

Selective adenosine agonists are undergoing clinical trials for?

A
  • Cardiac arrhythmias and pain (A1)
  • Cardiac imaging and inflammation (A2a)
  • Colon cancer, rheumatoid arthritis, psoriasis and dry eye (A3)
58
Q

What does adenosine do in the hippocampus?

A

Attenuates LTP, adenosine agents mght be used in treatment of memory disorders

Molecular Neuroscience I (8 decks)

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