Crystalline serotonin

MM Rapport, AA Green, IH Page - Science, 1948 - science.org
MM Rapport, AA Green, IH Page
Science, 1948science.org
Very few substances capable, at high dilution, of effecting changes in the caliber of blood
vessels have been isolated from normal animal tissues. These are epinephrine, histamine,
adenylic acid, acetylcholine, and choline. There are, however, several which, by their
pharmacological actions, are known to be present although their identity has remained
obscure. One of these is the vasoconstrictor which is present in serum and defibrinated
blood and which appears in connection with platelet destruction and the clotting process …
Very few substances capable, at high dilution, of effecting changes in the caliber of blood vessels have been isolated from normal animal tissues. These are epinephrine, histamine, adenylic acid, acetylcholine, and choline. There are, however, several which, by their pharmacological actions, are known to be present although their identity has remained obscure. One of these is the vasoconstrictor which is present in serum and defibrinated blood and which appears in connection with platelet destruction and the clotting process.
Although the presence of the substance, as revealed by the ability of serum to cause vasoconstriction in organs through which it is perfused, has been recognized for almost 80 years, its physiological function is not yet clearly defined. The isolation of this substance may lead to clarification of its role as a hemostatic agentin intra-vascular clotting and in cases, such as myocardial in-farction following coronary thrombosis, where the pre-vention of spread of hemorrhage into tissues is important. We are reporting the isolation of a crystalline sub-stance from beef serum which may be responsible for the vasoconstrictor activity. The details of the partial purification involving the following five steps have al-ready been reported (3): precipitation of serum proteins with ethyl alcohol; precipitation of inorganic salts, phos-phatides, and amino acids with acetone; removal of chloroform-soluble impurities; extraction of the active principle with butyl alcohol froman aqueous solution saturated with ammonium sulfate; and precipitation of the active substance from the butyl alcohol with 5-nitrobarbituric acid. Isolationwas attained withtwo addi-tional steps. The 5-nitrobarbiturate complex was decomposed by the addition ofacetone to its hot, saturated aqueous solution, and the precipitate was discarded. The filtrate was evaporated to dryness, and the residue was then extracted with warm absolute methanol. On cool-ing, this extract deposited clusters of prisms of the crude substance which, on recrystallization from water-acetone, formed thin, rhomboid, pale-yellow platelets (Fig. 1) melting at 207-2120 (corr.) with decomposition (effer-vescence) on the Kofier micro hot-stage. The purest sample thus far obtained melted at 212-2140 (corr.) with decomposition. The melting point behavior, despite the decomposition, closely parallels the degree of purity as determined by activity and colorimetric measurements. The general behavior of the crystalline substance is suggestive of its homogeneity. We would like provision-ally to name it serotonin, which indicates that its source is serum and its activity is one of causing constriction.
AAAS