TY - JOUR
T1 - Aldose reductase, a key enzyme in the oxidative deamination of norepinephrine in rats
AU - Kawamura, Minoru
AU - Eisenhofer, Graeme
AU - Kopin, Irwin J.
AU - Kador, Peter F.
AU - Lee, Yong S.
AU - Tsai, Jen Yue
AU - Fujisawa, Shigeki
AU - Lizak, Martin J.
AU - Sinz, Andrea
AU - Sato, Sanai
PY - 1999/8/1
Y1 - 1999/8/1
N2 - The sympathoneural neurotransmitter norepinephrine (NE) is deaminated to 3,4-dihydroxymandelaldehyde (DHMAL) and subsequently converted to either 3,4-dihydroxymandelic acid (DHMA) or 3,4-dihydroxyphenylglycol (DHPG). In this study, we investigated the relative importance of aldose reductase versus aldehyde reductase in the formation of DHPG from DHMAL. The in vitro incubation of NE with aldose reductase in the presence of monoamine oxidase (MAO) resulted in the formation of DHPG, which was confirmed by mass spectrometry. Although aldehyde reductase also generated DHPG, its activity was much lower than that of aldose reductase. With northern blotting, the expression of both aldose reductase and aldehyde reductase was detected in rat superior cervical ganglia. However, with western blotting, only aldose reductase was immunologically detectable. Treatment of rats with aldose reductase inhibitors for 3 days increased the plasma level of DHMA. There was no correlation between the selectivity of inhibitors and effects on NE metabolite levels. A significant decrease in DHPG, however, was obtained only with an extremely high dose (9 mg/kg/day) of the nonselective inhibitor AL 1576. The present study confirmed that aldose reductase generates DHPG from NE in the presence of MAO. In rat sympathetic neurons, aldose reductase appears to be more important than aldehyde reductase for the formation of DHPG. However, when aldose reductase is inhibited, it appears that aldehyde reductase can compensate for the conversion of DHMAL to DHPG, indicating redundancy in the reduction pathway. Copyright (C) 1999 Elsevier Science Inc.
AB - The sympathoneural neurotransmitter norepinephrine (NE) is deaminated to 3,4-dihydroxymandelaldehyde (DHMAL) and subsequently converted to either 3,4-dihydroxymandelic acid (DHMA) or 3,4-dihydroxyphenylglycol (DHPG). In this study, we investigated the relative importance of aldose reductase versus aldehyde reductase in the formation of DHPG from DHMAL. The in vitro incubation of NE with aldose reductase in the presence of monoamine oxidase (MAO) resulted in the formation of DHPG, which was confirmed by mass spectrometry. Although aldehyde reductase also generated DHPG, its activity was much lower than that of aldose reductase. With northern blotting, the expression of both aldose reductase and aldehyde reductase was detected in rat superior cervical ganglia. However, with western blotting, only aldose reductase was immunologically detectable. Treatment of rats with aldose reductase inhibitors for 3 days increased the plasma level of DHMA. There was no correlation between the selectivity of inhibitors and effects on NE metabolite levels. A significant decrease in DHPG, however, was obtained only with an extremely high dose (9 mg/kg/day) of the nonselective inhibitor AL 1576. The present study confirmed that aldose reductase generates DHPG from NE in the presence of MAO. In rat sympathetic neurons, aldose reductase appears to be more important than aldehyde reductase for the formation of DHPG. However, when aldose reductase is inhibited, it appears that aldehyde reductase can compensate for the conversion of DHMAL to DHPG, indicating redundancy in the reduction pathway. Copyright (C) 1999 Elsevier Science Inc.
KW - 3,4-dihydroxymandelaldehyde
KW - 3,4-dihydroxyphenylglycol
KW - Aldehyde reductase
KW - Aldose reductase
KW - Norepinephrine
KW - Sympathetic nervous system
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U2 - 10.1016/S0006-2952(99)00121-5
DO - 10.1016/S0006-2952(99)00121-5
M3 - Article
C2 - 10424772
AN - SCOPUS:0032973893
SN - 0006-2952
VL - 58
SP - 517
EP - 524
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 3
ER -