Radioisotopic studies of the binding, exchange, and distribution of 5-hydroxytryptamine synthesized from its radioactive precursor.

1. The synthesis, distribution, storage, and subsequent metabolism of 5-hydroxytryptamine (5-HT) produced in mice from the administration of its radioactive precursor, 5-hydroxytryptophan, has been investigated to form the basis for a similar study to be conducted by radioautography.2. Intravenous injection of the radioactive material was found to be essential for significant uptake of radioactivity by tissue. The duration of the period during which radioactive material was available for uptake by the tissue was 2 hr.3. The relative distribution of radioactivity in individual organs was studied and the radioactive compounds present in each were identified and quantitatively assayed. No unrelated routes of metabolism of the labelled material were found and radioautographic results may be interpreted in terms of the metabolic picture which emerged.4. Radioactive 5-HT was bound in tissues in preference to both its precursor, and metabolite, 5-hydroxytryptamine-O-glucuronide, and the radioactive 5-HT produced in vivo after the injection of labelled 5-hydroxytryptophan probably entered and labelled the endogenous 5-HT pool.5. Fixatives prepared with buffer solutions made hypertonic by the addition of sucrose could rapidly and effectively halt the movement of radioactive 5-HT out of tissues and prevent its subsequent extraction during histological processing.6. It is concluded that localization of sites concerned with 5-HT metabolism by means of radioautography is feasible and the 5-HT so localized will probably reflect the physiological compartmentalization of the amine.