Release and metabolism of 5-hydroxytryptamine in the cat spinal cord examined with microdialysis.
The primary objective of this work was to investigate how in vivo administration of depolarizing agents increases extracellular concentrations of 5-hydroxytryptamine (5-HT) and simultaneously decreases levels of its chief metabolite 5-hydroxyindole-3-acetic acid (5-HIAA). To this end the effects of a number of agents on extracellular levels of 5-HT and 5-HIAA in cat spinal cord were determined by microdialysis and high-pressure liquid chromatography with electrochemical detection. The semipermeable portion of the dialysis probe was centered in the dorsal horn. Artificial cerebrospinal fluid containing elevated K+ or drugs was introduced into the dorsal horn via the dialysis probe. Increases in recovered 5-HT were assumed to reflect increased levels in the extracellular fluid due to release, reduced reuptake and/or reduced metabolism. Depolarizing agents (K+, veratridine and aconitine) increased 5-HT, but dramatically decreased 5-HIAA levels. Extracellular 5-HT returned to near base-line levels with removal of the depolarizing agents. The reduction in 5-HIAA was transient after potassium infusion, but outlasted the infusion of veratridine or aconitine by several hours. Reduction of 5-HIAA could be blocked or reversed with the Na+ channel blockers, lidocaine and tetrodotoxin. Evidently, the decrease in 5-HT metabolism followed activation of sodium channels. Parachloroamphetamine caused an increase in 5-HT levels, presumably reflecting increased 5-HT release, but did not change 5-HIAA levels. Although fluoxetine increased 5-HT, it reduced 5-HIAA, presumably through blockade of 5-HT reuptake leading to a secondary reduction in metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Sorkin
L S
LS
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston.
Hughes
M G
MG
Liu
D
D
Willis
W D
WD
McAdoo
D J
DJ
D000157:Aconitine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003956:Dialysis; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D005473:Fluoxetine; D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D014701:Veratridine; D011188:Potassium; D000157:Aconitine