Oxidation of the Indole Nucleus of 5-Hydroxytryptamine and the Formation of Pigments: Isolation and Partial Characterization of a Dimer of 5-Hydroxytryptamine

Abstract

The products of the metabolism of 5-hydroxytryptamine are of interest not only because of their possible physiological importance but also because of their pathological potentialities. Although the oxidation of the ethylamine portion of the molecule has been extensively investigated (1) only suggestions have been made concerning oxidation of the indole nucleus: Dalgliesh (2) has proposed that 5-hydroxytryptamine may be metabolized to a substance of enhanced physiological activity, e.g. 5,6or 4,5-dihydroxytryptamine; and Udenfriend et al. (1) have suggested that melanin-like pigments may be derived from tryptophan by way of a 5,6-dihydroxyindole. McIsaac and Page (3) have found in the urine of rabbits and rats given radioactive 5-hydroxytryptamine a minor metabolite, provisionally identified as an oxidation product and diagrammatically represented as an o-dihydroxytryptamine; apparently the same compound, referred to only as a hydroxyindole, was found in liver tumor tissue and in the urine of a patient who had the carcinoid syndrome associated with a malignant bronchial adenoma (4). As a part of a general investigation of the properties of 5-hydroxytryptamine related to its histochemistry (5) and its participation in some pathologic processes (6) we have studied the oxidation products formed from this substance by a serum enzyme, by molecular oxygen, and by silver ion. The latter was used because it readily oxidizes 5-hydroxytryptamine histochemically. The following is a report of our studies of the oxidation products formed by the two inorganic reagents, and includes the isolation and partial characterization of a dimer of 5-hydroxytryptamine identical in chromatographic mobility and color reactions with one of the products observed in the oxidation of 5-hydroxytryptamine by the action of a human serum oxidase (7) .I