Myocardial interstitial serotonin and its major metabolite, 5-hydroxyindole acetic acid levels determined by microdialysis technique in rat heart

Aims: The aim of this study was to elucidate myocardial interstitial serotonin (5-HT) kinetics in the heart, including 5-HT reuptake and enzymatic degradation to 5-hydroxyindole acetic acid (5-HIAA) via monoamine oxidase (MAO). Main methods: Using microdialysis technique in anesthetized rats, we simultaneously monitored myocardial interstitial levels of 5-HT and its major metabolite, 5-HIAA, in the left ventricle and examined the effects of local administration of a MAO inhibitor, pargyline, or a 5-HT uptake inhibitor, fluoxetine. Key findings: Pargyline increased dialysate 5-HT concentration from 1.8 +/- 0.3 at baseline to 3.9 +/- 0.5 nM but decreased dialysate 5-HIAA concentration from 20.7 +/- 1.0 at baseline to 15.8 +/- 1.4 nM at 60-80 min of administration. Fluoxetine increased dialysate 5-HT concentration from 1.9 +/- 0.4 at baseline to 6.5 +/- 0.9 nM at 60-80 min of administration, but did not change dialysate 5-HIAA concentration. Local administration of ADP (100 mM) increased dialysate 5-HT and 5-HIAA concentrations. Pargyline did not affect ADP-induced increase in dialysate 5-HT concentration but suppressed ADP-induced increase in dialysate 5-HIAA concentration during 60 min of ADP administration. Fluoxetine increased dialysate 5-HT concentration at 40-60 min of ADP administration, but did not affect ADP-induced increase in dialysate 5-HIAA concentration. Significance: Simultaneous monitoring of myocardial interstitial 5-HT and 5-HIAA levels provides valuable information on 5-HT kinetics including reuptake and enzymatic degradation by MAO, which play a role in the regulation of myocardial interstitial 5-HT levels at baseline and when 5-HT levels are elevated. (C) 2014 Elsevier Inc. All rights reserved.