Effect of Serotonin on Glycogen Metabolism in Isolated Rat Liver*

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Abstract
Endoportal administration of serotonin creatinine sulfate, in doses as low as 410-4 [image], or endogenously synthesized serotonin derived from administered 5-hydroxytryptophan (210-2 [image]), produced glycogenolysis, hyperglycemia, and stimulation of hepatic phosphorylase activity in the isolated perfused rat liver. These actions of serotonin were independent of observed vasomotor effects of the amine on the liver. Tachyphylaxis was notable in this preparation with regard to the effect of serotonin on hepatic blood flow. Unlike exogenous serotonin, 5-hydroxytryptophan had no effect on hepatic blood flow although it induced glycogenolysis to a degree similar to the exogenously administered amine. The glycogenolytic and vasomotor actions of the amine were blocked by the infusion of a potent serotonin antagonist, l-methyl-(methylergono-vine), before serotonin administration. The glycemic effect observed in vitro was also noted in vivo when intact rats received parenteral serotonin or 5-hydroxytryptophan. Hepatic uptake of serotonin by the isolated liver was significant in the steady state and after rapid serotonin injection, but the capacity of the liver to clear the infused amine was limited and exceeded after 3 hours of continuous serotonin infusion.