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Final Biochemistry > Serotoninergic Neurotransmission > Flashcards

Serotoninergic Neurotransmission Flashcards

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

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

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

17
Q

Diurnal rhythm

A

M1a receptor -> Pituitary gland

M1b receptor -> Suprachiamstic nucleus

18
Q

Serotonin transport on vesicles

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

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

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?

A
  • Cocaine

- TCA (tricyclic antidepressants)

22
Q

How many Serotonin receptors are there?

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

Agonist of 5-HT1 Receptors

A

5-CT
8-OH-DPAT
Sumatriptan

24
Q

Antagonist of 5-HT1 Receptors

A

Spiperone

25
Q

Molecular effects of 5-HT1 Receptors

A

Gi –> decrease cAMP

26
Q

Agonist of 5-HT 2 receptors?

A
  • LSD

- a-methyl- 5-HT

27
Q

Antagonists of 5-HT 2 receptors?

A
  • ketanserin
  • cyproheptadine
  • LSD
  • methysergide
28
Q

Moleculare mechanism of 5-HT 2 receptors?

A

Gq –> Ip3/ DAG

29
Q

Location of type 1 receptors

A
  • blood vessels

- heart

30
Q

location of type 2 receptors

A
  • smooth muscle
  • platlets
  • cns/pns
  • gi tract
31
Q

location of type 3 receptors

A

cns and pns

32
Q

mechanism of the 5-HT 3 receptors

A

ligand-gated cation channel

-found to induce vomitting when agonised

33
Q

mechanism of 5-HT 4 and 7 receptors?

A

Gs -> increase cAMP

34
Q

Anti-depressant drugs

A

1) MAO-A inhibitions -> SELEGILINE (deprenyl).
2) SSRI and TCA -> SERT Inhibitiors
3) 5-HT 1a receptor agonists (Buspirone, flesinox)

35
Q

Anti-physcotic drugs

A

schizophrenia and bipolar disease.

5-HT 2 a/b receptor antagonists –> olanzipine (zyprexia)

LSD = 5-ht 2 a/b AGONIST so induces hallucinations

36
Q

cause of nausea

A

chemotherapy -> sero release from enterochromaffin cells -> visceral afferent neurons 5-ht3 receptors -> depolarisation —> chemoreceptoractivation —> nausea

37
Q

drugs for nausea

A

5-ht 3 receptor antagonist.

i.e// ondansetron

38
Q

cause of migrane

A

decrease in serotinonergic activity -> vasoconstriction of vessels in the brain -> severe pain

39
Q

drug for migrane

A

5-ht 1/b/d agonist —> sumatriptin.

Final Biochemistry (5 decks)

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