Effect of lithium on norepinephrine metabolic pathways.
We investigated lithium-induced changes in norepinephrine (NE) catabolism. NE and its major metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenyl glycol (DHPG), ions such as lithium (Li(+)), magnesium (Mg(2+)), and potassium (K(+)) were measured in rat plasma and cerebral cortex using an HPLC method with electrochemical detection for amines. The results obtained with a group of rats treated by lithium chloride (2 mmol/kg/IP) were compared with a control group receiving sodium chloride (2 mmol/kg/IP). Animals were killed at different times over a period of six hours in the morning following salt administration to minimize possible chronobiological effects. There are two pathways leading to MHPG formation: way A, without DHPG, and way B, with DHPG. In plasma and cerebral cortex of lithium treated rats, way A catabolism seems to be preferential. Lithium increases Mg(2+) and K(+) plasma levels. These results suggest that lithium may increase inactivation of NE and decrease NE available for adrenergic receptors.
Sastre
E
E
Laboratoire de Chimie Analytique, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France. elisabeth.sastre@pharmacie.univ-mrs.fr
Nicolay
A
A
Bruguerolle
B
B
Portugal
H
H
D000818:Animals; D019540:Area Under Curve; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005260:Female; D008094:Lithium / Q000097:blood / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D008274:Magnesium / Q000097:blood / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013053:Spectrophotometry
D012965:Sodium Chloride; D008734:Methoxyhydroxyphenylglycol; D008094:Lithium; D018021:Lithium Chloride; D008274:Magnesium; D011188:Potassium; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine