ラット脳内アミン含量および肝Tryptophan PyrrolaseならびにTyrosine AminotransferaseにおよぼすPyridylalanine Analogs, GlycyrrhizinおよびCortisoneの影響

抄録

1. Chronic administration of cortisone (12.5 mg/kg/day, s.c., 7 days) activated liver tryptophan pyrrolase (TP) and decreased 5-hydroxytryptamine (5-HT) content of the brain in adrenalectomized rats. In contrast, dl-pyridylalanine analogs (2-PA, 3-PA and 4-PA) decreased liver TP activity and increased brain 5-HT in both of adrenalectomized and intact rats. Simultaneous administration of 2-PA or 3-PA (100 mg/kg) with cortisone (12.5 mg/kg) clearly inhibited the induction of TP in the liver but also the decrease of brain 5-HT by cortisone. The inhibitory potency of 4-PA to the above actions of cortisone was weaker than that of the other PA analogs. Glycyrrhizin (GL, 100 mg/kg) also inhibited the actions of cortisone, while GL did not affect liver TP activity and brain 5-HT content when administered singly to rats. 2. Chronic administration of 2-PA or 3-PA increased liver tyrosine aminotransferase (TA) activity in both of adrenalectomized and intact rats. Liver TA activity in adrenalectomized rats was more potently activated by simultaneous administration of 2-PA or 3-PA (100 mg/kg) with cortisone (12.5 mg/kg) compared with any single administration of these compounds ; the effects were additive. 4-PA (150 mg/kg) decreased liver TA activity and slightly inhibited the induction of this enzyme by cortisone. A simultaneous administration of GL (100 mg/kg) with cortisone clearly inhibited the action of cortisone, but a single administration of GL hardly affected TA activity. Brain norepinephrine (NE) content in adrenalectomized and intact rats did not alter after single or simultaneous administration of these compounds. 3. These data suggest that alterations of liver TP activity can lead to changes in brain 5-HT content and that the altered liver TA activity is unrelated to brain NE content. The results indicate that PA analogs increase brain 5-HT content without affecting NE content in rats.