Uptake and metabolism of serotonin by rat adrenal tissue in vitro

After incubation of separate zones of rat adrenals with radioactively labelled serotonin--at concentrations at which the amine had been previously shown to stimulate aldosterone biosynthesis--the tissue radioactivity was several times higher in the capsular ("zona glomerulosa") than in the decapsulated portions of the glands. High doses of unlabelled serotonin diminished the accumulation of radioactivity, but only when added simultaneously with the tracer. In the course of the incubation, radioactive 5-hydroxy-3-indoleacetic acid, i.e. the deaminated metabolite of serotonin, rapidly appeared in the medium. Most of the radioactive material accumulated by the adrenal was recovered in the cytosol fraction and was no longer identical with serotonin, but consisted mainly of 5-hydroxy-3-indoleacetic acid and another, unidentified metabolite. Unaltered serotonin was found in capsular adrenal tissue extracts only when a monoamine oxidase inhibitor (nialamide) has been added to the incubation medium. Rapid uptake and metabolism thus appeared to be the predominant features of the interaction of incubated adrenal tissue with serotonin. These events may have obscured the possible binding of very small amounts of serotonin to receptor sites. The observed accumulation of radioactivity in adrenal tissue was mainly due to delayed outflow of intracellulary formed metabolite, since 5-hydroxy-3indoleacetic acid was neither taken up by incubated adreanls nor bound by adrenal cytosol. No evidence of serotonin storage in the zona glomerulosa was found in these studies.