Body distribution of infused serotonin in rats

Clin Exp Pharmacol Physiol. 2009 May;36(5-6):599-601. doi: 10.1111/j.1440-1681.2009.05147.x. Epub 2009 Jan 18.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biological Availability
  • Drug Evaluation, Preclinical
  • Infusion Pumps
  • Male
  • Rats
  • Rats, Transgenic
  • Rats, Wistar
  • Serotonin / administration & dosage
  • Serotonin / pharmacokinetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Tissue Distribution

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Serotonin