TY - JOUR
T1 - Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans
AU - Eisenhofer, Graeme
AU - Åneman, Anders
AU - Hooper, Douglas
AU - Rundqvist, Bengt
AU - Friberg, Peter
PY - 1996/4
Y1 - 1996/4
N2 - This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3- methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), comprised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate- conjugated 3-methoxy-4-hydroxyphenylglycol.
AB - This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3- methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), comprised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate- conjugated 3-methoxy-4-hydroxyphenylglycol.
KW - Kidneys
KW - Liver
KW - Metabolism
KW - Norepinephrine
KW - Sympathetic nerves
UR - http://www.scopus.com/inward/record.url?scp=0029874309&partnerID=8YFLogxK
M3 - Article
C2 - 8627312
AN - SCOPUS:0029874309
SN - 0022-3042
VL - 66
SP - 1565
EP - 1573
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -