title: Myocardial interstitial serotonin and its major metabolite, 5-hydroxyindole acetic acid levels determined by microdialysis technique in rat heart.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  Pargyline increased dialysate 5-HT concentration from 1.8±0.3 at baseline to 3.9±0.5nM but decreased dialysate 5-HIAA concentration from 20.7±1.0 at baseline to 15.8±1.4nM at 60-80min of administration. Fluoxetine increased dialysate 5-HT concentration from 1.9±0.4 at baseline to 6.5±0.9nM at 60-80min of administration, but did not change dialysate 5-HIAA concentration. Local administration of ADP (100mM) 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 60min of ADP administration. Fluoxetine increased dialysate 5-HT concentration at 40-60min of ADP administration, but did not affect ADP-induced increase in dialysate 5-HIAA concentration.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. Electronic address: duchk@ri.ncvc.go.jp.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Du
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Zhan
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000818:Animals; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010293:Pargyline / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000244:Adenosine Diphosphate; D005473:Fluoxetine; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Anesthetized rat; Cardiac serotonin; Microdialysis technique