In addition to similarities in neuronal organization, monoaminergic systems are similar with regard to their synthesis, storage, and degradation. Monoamines are synthesized within neurons from common amino acid precursors and taken up into synaptic vesicles via a vesicular monoamine transporter. Upon stimulation, vesicles within nerve terminals release neurotransmitter into the synaptic cleft. Once released, the monoamines interact with postsynaptic receptors to alter the excitability of postsynaptic cells. Monoamines may also interact with presynaptic autoreceptors located on the nerve terminal to suppress further release. In addition, released monoamines may be taken back up from the synaptic cleft into the nerve terminal by plasma membrane transporter proteins. Reuptake plays an important role in limiting the magnitude and duration of action of synaptically released monoamines. Once monoamines are taken up, they may be subject to enzymatic degradation or they may be protected from degradation by uptake into vesicles. The processing of acetylcholine differs from this scheme, and is described below.
[...] Two enzymes that play major roles in the degradation of catecholamines are monoamine oxidase and catechol O-methyltransferase (COMT). Monoamine oxidase is located on the outer membrane of mitochondria and oxidatively deaminates catecholamines to their corresponding aldehydes. Two MAO isozymes with differing substrate specificities have been identified: MAOA, which preferentially deaminates serotonin and norepinephrine, and MAO type B (MAOB), which deaminates dopamine, histamine, and a broad spectrum of phenylethylamines. The blockade of monoamine catabolism by MAOIs produces elevations in brain monoamine levels. [...]
[...] The first step in the degradation of serotonin is mediated by monoamine oxidase (MAO) type A. A (MAOA), which oxidizes the amino group to form an aldehyde. MAOA is located in mitochondrial membranes and is nonspecific in its substrate specificity; in addition to serotonin, it oxidizes norepinephrine. The elevation of serotonin levels by MAO inhibitors (MAOIs) is believed to underlie the antidepressant efficacy of these drugs. Following oxidation by MAOA, the resulting aldehyde is further oxidized to 5-hydroxyindoleacetic acid (5-HIAA). [...]
[...] The transport and storage of monoamines in vesicles may serve several purposes: to enable the regulated release of transmitter under appropriate physiological stimulation, to protect monoamines from degradation by MAO, and to protect neurons from the toxic effects of free radicals produced by the oxidation of cytoplasmic monoamines. In contrast with the plasma membrane transporters, a single type of vesicular monoamine transporter is believed to mediate the uptake of monoamines into synaptic vesicles within the brain. Consistent with this, blockade of this vesicular monoamine transporter by the antihypertensive drug reserpine (Serpasil) has been found to deplete brain levels of serotonin, norepinephrine, and dopamine. [...]
[...] In humans the predominant metabolites of dopamine and norepinephrine are homovanillic acid (HVA) and 3-methoxy-4- hydroxyphenylglycol (MHPG), respectively. Histamine As is the case for serotonin, the brain contains only a small portion of the histamine found in the body. Histamine is distributed throughout most tissues of the body, predominantly in mast cells. Because it does not readily cross the blood-brain barrier, histamine is believed to be synthesized within the brain where it is formed by the decarboxylation of the amino acid histidine by a specific histidine decarboxylase. [...]
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