Week 7 Serotonin, Histamine, GABA, and Glycine Flashcards Preview

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Flashcards in Week 7 Serotonin, Histamine, GABA, and Glycine Deck (17)
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Describe the biosynthesis of serotonin.

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


How is melatonin produced?

From serotonin pathway
-Serotonin-->N-acetyl serotonin-->melatonin


What is the distribution of serotonin in the body?

-only 1-2% in the brain
-gut, pineal gland, midline or raphe regions of pons and upper brain stem rich in serotonin


What are some agonist and antagonists of serotonin receptors?

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


What is the mechanism of MDMA (ecstasy)?

-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


Where is histamine produced in the brain? in body?

-tuberomammilary nucleus of hypothalamus
-mast cells


Describe the biosynthesis of histamine

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


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

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


What are effects of histamine on the body?

-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


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

Glutamate-->GABA by GAD (glutamic acid decarboyxlase) = regulatory event
-linked to Krebs cycle
-glial cells participate in GABA metabolism and recycling


How is serotonin broken down?

By MAO and aldehyde dehydrogenase to 5-HIAA


What are some agonist and antagonist of GABA receptors?

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


What is gamma hydroxybutyrate (GHB)?

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


Where is glycine normally found? (neurotransmitter)

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


Describe the biosynthesis and catabolism of glycine.

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


Describe glycine receptors.

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


What is the human startle disease?

-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

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