title: Myocardial interstitial levels of serotonin and its major metabolite 5-hydroxyindole acetic acid during ischemia-reperfusion.
abstract: The aim of this study was to examine the accumulation of serotonin (5-HT) and degradation of 5-HT taken up into cells in the ischemic region during myocardial ischemia-reperfusion. Using microdialysis technique in anesthetized rats, we monitored myocardial interstitial levels of 5-HT and its metabolite produced by monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5-HIAA), during 30-min coronary occlusion followed by 45-min reperfusion, and investigated the effects of local administration of the MAO inhibitor pargyline and the 5-HT uptake inhibitor fluoxetine. In the vehicle group, the dialysate 5-HT concentration increased from 1.3 ± 0.2 nM at baseline to 29.6 ± 2.8 nM at 22.5-30 min of occlusion, but the dialysate 5-HIAA concentration did not change from baseline (9.9 ± 1.1 nM). Upon reperfusion, the dialysate 5-HT concentration increased further to a peak (34.2 ± 4.2 nM) at 0-7.5 min and then declined. The dialysate 5-HIAA concentration increased to 31.9 ± 5.2 nM at 7.5-15 min of reperfusion and maintained this high level until 45 min. Pargyline markedly suppressed the increase in dialysate 5-HIAA concentration after reperfusion and increased the averaged dialysate 5-HT concentration during the reperfusion period. Fluoxetine suppressed the increase in dialysate 5-HT concentration during occlusion but did not change dialysate 5-HT or 5-HIAA concentration after reperfusion. During ischemia, 5-HT secreted from ischemic tissues accumulates but 5-HT degradation by MAO is suppressed. After reperfusion, degradation of 5-HT taken up into cells is enhanced and contributes to the clearance of accumulated 5-HT. This degradation following cellular uptake is dependent on MAO activity but not the fluoxetine-sensitive uptake transporter.
  By monitoring myocardial interstitial levels of 5-HT and its metabolite, 5-hydroxyindole acetic acid, we investigated 5-HT kinetics during myocardial ischemia-reperfusion. 5-HT accumulates but 5-HT degradation is suppressed during ischemia. After reperfusion, 5-HT degradation is enhanced and this degradation is dependent on monoamine oxidase activity but not fluoxetine-sensitive uptake transporter.
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and duchk@ncvc.go.jp.
authors: Cheng-Kun
authors: http://orcid.org/0000-0002-7955-6938
authors: CK
authors: Du
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and.
authors: Dong-Yun
authors: DY
authors: Zhan
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and.
authors: Tsuyoshi
authors: T
authors: Akiyama
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and.
authors: Tadakatsu
authors: http://orcid.org/0000-0002-2639-199X
authors: T
authors: Inagaki
authors: Department of Research Promotion, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors: Toshiaki
authors: T
authors: Shishido
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and.
authors: Mikiyasu
authors: M
authors: Shirai
authors: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; and.
authors: James T
authors: http://orcid.org/0000-0002-3318-5406
authors: JT
authors: Pearson
mesh_terms: D000818:Animals; D054059:Coronary Occlusion / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D005473:Fluoxetine; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: SERT; anesthetized rat; cardiac serotonin; extraneuronal monoamine transporter; microdialysis technique