Week 7 Serotonin, Histamine, GABA, and Glycine

Question 1

Describe the biosynthesis of serotonin.

Answer 1

1. Tryptophan (TRP) is precursor
   -levels have daily rhythm, as do 5-HT
   -converted by tryptophan hydroxylase (TPH)
   =rate-limiting step
   -inhibited by p-chlorophenylalanine
2. 5-hydroxytryptophan–>serotonin
   enzyme: 5-HTP decarbxylase

Question 2

How is melatonin produced?

Answer 2

From serotonin pathway

-Serotonin–>N-acetyl serotonin–>melatonin

Question 3

What is the distribution of serotonin in the body?

Answer 3

• only 1-2% in the brain

- gut, pineal gland, midline or raphe regions of pons and upper brain stem rich in serotonin

Question 4

What are some agonist and antagonists of serotonin receptors?

Answer 4

Agonist
-psilocybin, mescaline, LSD
Antagonist
-reserpine interferes with reuptake
-SSRI such as Prozac

Question 5

What is the mechanism of MDMA (ecstasy)?

Answer 5

• indirect agonist that releases 5-HT
• use may reduce availability of 5-HT for long periods (months)
• adverse events: paranoia, permanent loss of serotonergic neurons

Question 6

Where is histamine produced in the brain? in body?

Answer 6

• tuberomammilary nucleus of hypothalamus

- mast cells

Question 7

Describe the biosynthesis of histamine

Answer 7

• precursor: Histidine
• enzyme: histidine decarboxylase
• metabolized by histamine methyl transferase

Question 8

What are the histamine receptors and what do some pharmacological applications?

Answer 8

1. H-1: causes bronchoconstriction. Anti-histamines block for bronchodilation
2. H-2 antagonist used to decrease gastric juices
3. H-3 autoreceptors. Antagonists may increase wakefulness
4. H-4 on leukocytes

Question 9

What are effects of histamine on the body?

Answer 9

• hypotension and bronchoconstriction
• may alter food and water intake in hypothalamus
• role in arousal, H-1 antagonist may have sedative effects
• prolonged use of antihistamines may contribute to alzheimer like syndromes

Question 10

Describe the biosynthesis of GABA (gamma-aminobutyric acid).

Answer 10

Glutamate–>GABA by GAD (glutamic acid decarboyxlase) = regulatory event

• linked to Krebs cycle
• glial cells participate in GABA metabolism and recycling

Question 11

How is serotonin broken down?

Answer 11

By MAO and aldehyde dehydrogenase to 5-HIAA

Question 12

What are some agonist and antagonist of GABA receptors?

Answer 12

Agonist
-Bendiazepam (Valium) (Gaba A)
-baclofen (gaba B receptor)
Antagonist
-Bicuculline (convulsant)
-Picrotoxin-non competitive inhibitor that is antidote for barbiturates

Question 13

What is gamma hydroxybutyrate (GHB)?

Answer 13

• breakdown product of GABA
• liquid ecstasy, liquid X, GHB, etc
• toxicity: coma, seizures, vomiting, respiratory depression, amnesia

Question 14

Where is glycine normally found? (neurotransmitter)

Answer 14

• major inhibitory transmitter in the brain stem and spinal cord
• used by short axon interneurons usually
• also found in other places in the brain

Question 15

Describe the biosynthesis and catabolism of glycine.

Answer 15

• synthesized from serene and transported into synaptic vesicle
• glycine action destroyed by glycine cleavage system at neighboring astrocytes or recycled at presynaptic membrane

Question 16

Describe glycine receptors.

Answer 16

• GLY-R is chloride channel with 5 subunits
• antagonist: strychnine, a convulsant
• Picrotoxin-noncompetitive inhibitor of GLY-R

Question 17

What is the human startle disease?

Answer 17

• hereditary hyperekplexia
• distint overexcitability and diminished inhibition in patients with hyperekplexia
• overact to unexpected stimuli with myoclonic jerks and stiffness
• single bass mutation resulting in decrease in GLY affinity to receptors