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Catecholamines
Biosynthesis of Catecholamines
5. Catabolism
Dopa decarboxylase
1. Cofactor: pyridoxine; low Km but high Vmax 2. Also decarboxylate 5-HTP and other aromatic a.a.: aromatic amino acid decarboxylase (AAAD)
3. Inhibitor: -methyldopa
Dopamine -hydroxylase
1. Cofactor: ascorbate; substrate: dopamine
VMAT2:
Non-selective and has high affinity to reserpine
Metabolism of dopamine
Major acidic metabolites: A. 3,4-dihydroxy phenylacetic acid (DOPAC) B. Homovallic acid (HVA)
Inactivation of Norepinephrine
Catechol-O-methyltransferase (COMT)
1. Enzyme can metabolize both intra- or extracellularly 2. Requires Mg2+ and substrate of S-adenosylmethionine
Uptake transporters
1. Released catecholamines will be up-take back into presynaptic terminals (DAT, NET)
2. Transporter is a Na+ and Cl+-dependent process (ouabain [Na,K-ATPase inhibitor] and veratridine [Na channel open] block uptake process)
Dorsal bundle
Spinal cord cerebellum
Hypothalamus and Brainstem (Locus ceruleus)
Ventral bundle
Nigrostriatal projection
Substantia nigra to caudate/putamen n.
Tuberohypophysial projection
Hypothalamus to median eminence
Mesocotical projection
Ventral tegmental area to nucleus accumbens and frontal cortex
Catecholamine receptors
1. 2. Postsynaptic receptors locate on dendrites or cell body, axons or nerve terminals Presynaptic autoreceptors locate on the same neuron: a. terminal autoreceptor: control release b. somatodendritic autoreceptor: synthesis control c. major autoreceptor type: 2-adrenergic receptor in PNS/CNS; D2-dopamine receptor d. exception: -adrenergic receptor facilitates NE release
4. Chronic antagonist treatment up-regulate D2 receptors; agonist treatment might down-regulate the D2 receptor 5. Pharmacological application: anti-Parkinson (D2 agonist), anti-psychotic (D2 antagonist), addictive drugs (DA transporter)
propanolol
yohimbine
catecholamine receptor