Production of cysteinyl-dopamine during intravenous dopamine therapy.
BACKGROUND
Oxidized dopamine rapidly forms thiol-conjugates with --SH groups on cysteine, glutathione, and proteins. We used cysteinyl-dopamine production as an index of thioester production during intravenous dopamine treatment of critically ill patients.


METHODS
Cysteinyl-dopamine and catecholamines were measured by high-performance liquid chromatography with electrochemical detection. The production of cysteinyl-dopamine by purified human neutrophils was measured using dopamine (1 micromol/L) and cysteine (1 mmol/L) concentrations similar to those found during dopamine treatment. To examine the impact of endotoxic shock on cysteinyl-dopamine production, anesthetized rats were given dopamine (12 to 15 microg/kg/min intravenously) with or without endotoxin (50 mg/kg intravenously).


RESULTS
In vitro, neutrophils converted 26% of dopamine to cysteinyl-dopamine (30 min at 37 degrees C). Activating neutrophils with zymogen increased dopamine consumption from 26 to 68%, but only 36% appeared as cysteinyl-dopamine. The remainder may have been oxidized to other cysteinyl derivatives. Endotoxin increased cysteinyl-dopamine in rat plasma from 2.5 nmol/L (range <0.2 to 11) to 9.7 nmol/L (range <0.3 to 31, P = 0.1). After four hours, with or without endotoxin, cysteinyl-dopamine was <0.3 nmol/L in cerebrospinal fluid. In the plasma of eight patients receiving dopamine (6 to 20 microg/kg/min for 1 to 3 days), dopamine was 0.5 to 9.9 micromol/L, and cysteinyl-dopamine was 48 to 1660 nmol/L. Cysteinyl-dopamine was 4.3 to 22.6% of dopamine and correlated with leukocyte count (r(2) = 0.388, P = 0.099).


CONCLUSIONS
A significant fraction of exogenously administered dopamine reacts with -SH groups of cysteine and probably also with -SH groups on peptides and proteins. During brief dopamine treatment of endotoxic shock in rats, neither dopamine nor cysteinyl-dopamine crossed the blood-brain barrier.
Magnay
J L
JL
Department of Laboratory Medicine and Pathobiology, University of Toronto and The University Health Network, Toronto, Ontario, Canada.
Tong
J
J
Drangova
R
R
Baines
A D
AD
D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000652:urine; D003548:Cysteinyldopa / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000633:toxicity; D004298:Dopamine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology
C086394:5-S-glutathionyldopamine; D002395:Catecholamines; D003548:Cysteinyldopa; C047408:5-S-cysteinyldopamine; D004298:Dopamine