Monoamine oxidase type a: differences in selectivity towards l-norepinephrine compared to serotonin |
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Authors: | Nancy A Garrick Dennis L Murphy |
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Institution: | 1. Clinical Neuropharmacology Branch, NIMH, Bethesda, MD 20205, U.S.A.;2. Physiology Division, University of Maryland Deparment of Zoology, College Park, MD 20741, U.S.A. |
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Abstract: | l-Norepinephirine and serotonin have been regarded as preferential substrates for monoamine oxidase (MAO) type A. A close comparative examination of a number of tissues from different species, however, indicated the following differences. Serotonin was a more selective substrate for MAO-A, being inhibited by low concentrations (< 10-7M) of the irreversible MAO-A inhibitor, clorgyline, more consistently and to a greater extent (80–100%) than was l-norepinephrine (30–85%). These serotonin-norepinephrine differences were greater in humans and other primates than in rodents. Serotonin also had a 2- to 4-fold smaller apparent Km for MAO-A than l-norepinephrine and was deaminated 2- to 5-fold more readily by MAO in vitro in most tissues. In contrast, the MAO-B in human platelets deaminated l-norepinephrine more readily than serotonin. Thus, l-norepinephrine, like dopamine, should be regarded as a substrate for both MAO-A and MAO-B in vitro. The prominent role of MAO-B in norepinephrine degradation in primates may need to be considered in interpreting laboratory and clinical studies of clorgyline selective MAO-inhibiting drugs. |
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Keywords: | Address all correspondence to: Nancy A Garrick Clinical Neuropharmacology Branch National Institute of Mental Health NIH Clinical Center 10/3D41 Bethesda MD 20205 U S A |
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