Serotonin-Induced Swelling of Rat Liver Mitochondria

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dependence of the magnitude of serotonin creatinine sulfate-induced swelling upon the inducer concentration was evident down to 5×10-6M. Possibility of heavy metal contamination was excluded by the use of ash obtained after combustion of the serotonin preparation employed. Serotonin hydrochloride prepared by a novel Sephadex G-10 column method was shown to induce mitochondrial swelling. Sulfate or creatinine sulfate enhanced the swelling activity of serotonin. The time-course of serotonin-induced swelling simulated that of the swelling induced by NAD-linked substrate of mitochondrial oxidation. On a molar basis, serotonin was found to be more active than the NAD-linked substrates or some of the related indole derivatives. NAD-linked substrates interacted synergistically, and Ca2+ interacted additively with serotonin in the induction of swelling. Succinate markedly counteracted the serotonin effect. Serotonin-induced swelling was reversed by ATP, without an requirement of extraneous Mg2+. It was prevented by serum albumin, rotenone, amytal, antimycin A, dinitrophenol, and cyanide, but could not be prevented by a monoamine oxidase inhibitor β-isopropylphenylhydrazine. It differed from ascorbate-induced lysis in both the time course and magnitude. Ascorbate-induced mitochondrial lysis was prevented by serotonin. Dependence of serotonin-induced swelling on the NAD-branch of the respiratory chain was proposed and possible mechanism of the action was discussed.
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Serotonin-Induced Swelling of Rat Liver Mitochondria

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