Flashcards in Week 7 Serotonin, Histamine, GABA, and Glycine Deck (17)
Describe the biosynthesis of serotonin.
1. Tryptophan (TRP) is precursor
-levels have daily rhythm, as do 5-HT
-converted by tryptophan hydroxylase (TPH)
-inhibited by p-chlorophenylalanine
enzyme: 5-HTP decarbxylase
How is melatonin produced?
From serotonin pathway
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
Describe the biosynthesis of histamine
-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)
-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