FIGURE 6-6 Metabolism of catecholamines. Norepinephrine and epinephrine are first oxidatively deaminated by monoamine oxidase (MAO) to 3,4-dihydroxyphenylglycoaldehyde (DOPGAL) and then either reduced to 3,4-dihy-droxyphenylethylene glycol (DOPEG) or oxidized to 3,4-dihydroxymandelic acid (DOMA). Alternatively, they can be methylated initially by catechol-O- methyltransferase (COMT) to normetanephrine and metanephrine, respectively. Most of the products of either enzyme then are metabolized by the other enzyme to form the major excretory products in blood and urine, 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG or MHPG) and 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid, VMA). Free MOPEG is largely converted to VMA. The glycol and, to some extent, the O-methylated amines and the catecholamines may be conjugated to the corresponding sulfates or glucuronides.
displays a completely different profile of pharmacological inhibition. Other members of this family are OCT1 and OCT2 (see Chapter 2). In addition to catecholamines, OCT1-3 can transport other organic cations, including 5-HT, histamine, choline, spermine, guanidine, and creatinine.
RELEASE OF CATECHOLAMINES Details of excitation-secretion coupling in sympathetic neurons and the adrenal medulla are not completely known. The triggering event is the entry of Ca2+, which results in the exocytosis of the granular contents, including NE or Epi, ATP, some neuroactive peptides or their precursors, chromogranins, and D^H. Ca2+-triggered secretion involves interaction of molecular scaffolding proteins and fusion proteins, leading to docking of granules at the plasma membrane and thence to secretion (see Figure 6-5).
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