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Final Biochemistry > Serotoninergic Neurotransmission > Flashcards

Serotoninergic Neurotransmission Flashcards

(39 cards)

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1
Q

Role of Serotonin

A
  • Mood
  • Sleep
  • Apetite
  • Cognitive -> memory + learning
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2
Q

What produced Serotonin?

A

Raphe nuclei.

-located around the Reticular formation.

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3
Q

Caudal Raphe nuclie names

A
  • Magnus
  • Pallidus
  • Obscuris
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4
Q

Where do Caudal Raphe nuclie project to?

A
  • Cerebellum
  • Spinal cord
    • -> terminate onto the dorsal horn forming Enkephalins (inhibit pain sensation)
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5
Q

Rostral Raphe nuclie names?

A
  • pontis
  • median
  • dorsal
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6
Q

Where do Rostal Raphe nuclie project to?

A
  • Hypothalamus (Memory)
  • Thalamus
  • Cortex
  • Basal Ganglia
  • Suprachiasmatic nucleus (involved in feedback and regulation of Circadian cycle).
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7
Q

Synthesis of Serotonin steps

A

Tryptophan –1—> 5-HydroxyTryptophan —2—> Serotonin

1: Tryptophan Hydroxylase
2. Aromatic AA Decarboxylase

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8
Q

How does Tryptophan reach the brain?

A
  • Comes from food.
  • travels in plasma and enters the brain capillaries (forming blood-brain barrier) via:

Large Neutral AA Transporter (LAT1).

-this is identical transport for: Phe ,Leu , Met

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9
Q

Tryptophan Hydroxylase

A
  • In cytosol of Presynaptic neuron (only of serotoninergic neurons)
  • 50% similiar structure to —-Tyrosine Hydroxylase
  • Rate limiting step.
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10
Q

Km of Tryptophan Hydroxylase?

A

30-60 microM

thus low affinity, and enzyme is not saturated.

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11
Q

Regulation of Tryptophan Hydroxylase?

A

SHORT TERM:

-phosphorylation, increase activity (CMK II and PKC)

LONG TERM:

-increase in the synthesis of the enzyme

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12
Q

Inhibitor of Tryptophan Hydroxylase?

A

-Flencoline
(para-cholophenylalanaic -PCPA)\

irreversible inhibitor

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13
Q

Which co-factors are needed for Tryptophan Hydroxylase?

A
  • TetrahydroBIOPTERIN
  • O2
  • Iron
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14
Q

Metabolism of Serotonin

A
  • Done by MAO-A (on the outer mitochondrial membrane) +
  • Aldehyde Dehydrogenase

FORMS: –> 5-Hydroxyindoleactic Acid (5-HIAA)

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15
Q

Synthesis of Melatonin steps

A

Serotonin —1—-> N-Acetyl Serotonin —2—->Melatonin

1) 5-HT N-acetyl-transferase
2) 5-Hydroxyindole-O-methyltransferase

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16
Q

Regulation of Melatonin synthesis

Study These Flashcards
A
  • During day –> [melatonin] decreases
  • During Night—> B receptor stimulation –> cAMP increases.

cAMP causes activation of–: 5-HT N-actyltransferase.

17
Q

Diurnal rhythm

Study These Flashcards
A

M1a receptor -> Pituitary gland

M1b receptor -> Suprachiamstic nucleus

18
Q

Serotonin transport on vesicles

Study These Flashcards
A

VMAT 1/2:

  • 2H+, 5-HT ANTIPORTER (2 H+ for every sero entering).
  • H+ ATPase - ensures proton gradient (pH= 5.5)
19
Q

Serotonin reuptakes on pre-synaptic neuron

Study These Flashcards
A

SERT:

  • has 50% homology to NAT and DAT.
  • takes up Na+,Cl- and Serotonin.
  • can release K+ and Serotonin if high conc in the neuron.
20
Q

Inhibitors of Serotonin uptake into neuron

Study These Flashcards
A

Amphetamine Derivatives e.g//:

  • > Fenfluramine
  • > Ecstasy
  • > Reserpine
  • > Tetrabenzene

inhibition of VMAT- > SERT works in reverse and releases 5-HT

21
Q

Inhibitiors of SERT?

Study These Flashcards
A
  • Cocaine

- TCA (tricyclic antidepressants)

22
Q

How many Serotonin receptors are there?

Study These Flashcards
A
  • 1 (A,B,D)
  • 2 (A,B,C)
  • 3
  • 4
  • 5
  • 6
  • 7
23
Q

Agonist of 5-HT1 Receptors

Study These Flashcards
A

5-CT
8-OH-DPAT
Sumatriptan

24
Q

Antagonist of 5-HT1 Receptors

25
Molecular effects of 5-HT1 Receptors
Gi --> decrease cAMP
26
Agonist of 5-HT 2 receptors?
- LSD | - a-methyl- 5-HT
27
Antagonists of 5-HT 2 receptors?
- ketanserin - cyproheptadine - LSD - methysergide
28
Moleculare mechanism of 5-HT 2 receptors?
Gq --> Ip3/ DAG
29
Location of type 1 receptors
- blood vessels | - heart
30
location of type 2 receptors
- smooth muscle - platlets - cns/pns - gi tract
31
location of type 3 receptors
cns and pns
32
mechanism of the 5-HT 3 receptors
ligand-gated cation channel -found to induce vomitting when agonised
33
mechanism of 5-HT 4 and 7 receptors?
Gs -> increase cAMP
34
Anti-depressant drugs
1) MAO-A inhibitions -> SELEGILINE (deprenyl). 2) SSRI and TCA -> SERT Inhibitiors 3) 5-HT 1a receptor agonists (Buspirone, flesinox)
35
Anti-physcotic drugs
schizophrenia and bipolar disease. 5-HT 2 a/b receptor antagonists --> olanzipine (zyprexia) LSD = 5-ht 2 a/b AGONIST so induces hallucinations
36
cause of nausea
chemotherapy -> sero release from enterochromaffin cells -> visceral afferent neurons 5-ht3 receptors -> depolarisation ---> chemoreceptoractivation ---> nausea
37
drugs for nausea
5-ht 3 receptor antagonist. i.e// ondansetron
38
cause of migrane
decrease in serotinonergic activity -> vasoconstriction of vessels in the brain -> severe pain
39
drug for migrane
5-ht 1/b/d agonist ---> sumatriptin.

Final Biochemistry (5 decks)

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