Body distribution of infused serotonin in rats.
1. Our goal was to investigate the body distribution of serotonin (5-hydroxytryptamine; 5-HT) in rats infused with 5-HT (25 microg/kg per min) for 7 days and the contribution of the 5-HT transporter (SERT) for 5-HT uptake into the tissues. 2. Mini-osmotic pumps containing 5-HT or vehicle were implanted in rats knocked out for SERT (SERT-KO) or in wild-type (WT) rats. On the 8th day, tissues were harvested for measurements of 5-HT by high-performance liquid chromatography (HPLC). The 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) was also measured by HPLC, because an increase in 5-HIAA in tissues from rats receiving 5-HT reflects 5-HT uptake followed by metabolism. 3. In WT rats infused with 5-HT, an increase in 5-HT or 5-HIAA was observed in the heart, pancreas, thyroid, adrenal gland, kidney, seminal vesicle, bladder, prostate, liver, oesophagus, stomach, femur, trachea, lung and spleen compared with vehicle-infused rats. An increase in 5-HT and 5-HIAA was not observed in aorta, vena cava and jejunum. In tissues from SERT-KO rats infused with 5-HT, the content of 5-HT or 5-HIAA was decreased in most of the tissues studied compared with 5-HT-infused WT rats. Although 5-HT uptake in the kidney, seminal vesicle, prostate, jejunum and trachea is SERT dependent, it is SERT independent in the pancreas. The remaining tissues display SERT-dependent and -independent mechanisms for 5-HT uptake. 4. Altogether, tissues from different systems, such as the cardiovascular, endocrine, genitourinary and gastrointestinal, accumulate 5-HT mainly via SERT and, thus, these systems are potential targets for drugs that interfere with 5-HT homeostasis.
Linder
A Elizabeth
AE
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA. linderau@msu.edu
Beggs
Kevin M
KM
Burnett
Robert J
RJ
Watts
Stephanie W
SW
D000818:Animals; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical; D007260:Infusion Pumps; D008297:Male; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin