Effect of reserpine on histamine metabolism in the mouse brain

The effect of reserpine on brain histamine (HA) metabolism in vivo was examined in mice. The level of tele-methylhistamine, a major metabolite of HA, was decreased dose-dependently by reserpine (1-5 mg/kg s.c.), whereas the HA level was unaffected. This effect was observed in all brain regions examined. The accumulation of tele-methylhistamine induced by pargyline (65 mg/kg i.p.), an inhibitor of monoamine oxidase, was inhibited to 19% of the control value 24 hr after the treatment with reserpine (5 mg/kg s.c.). However, the HA decrease induced by (S)-alpha-fluoromethylhistidine (50 mg/kg i.p.) a specific inhibitor of histidine decarboxylase, was not significantly affected by pretreatment with reserpine (5 mg/kg s.c.) 1 or 24 hr before. The HA increase induced by metoprine (10 mg/kg i.p.), an inhibitor of histamine-N-methyltransferase, or by L-histidine (0.5-1.5 g/kg i.p.) was inhibited markedly by pretreatment with reserpine. This effect was more marked when reserpine was administered 1 hr than 24 hr before. In addition, the L-histidine-induced increase in HA level was enhanced markedly by the simultaneous administration of metoprine in the control mice but not in the mice treated with reserpine 1 hr before L-histidine injection. From these results the following are suggested. 1) There may be both of reserpine-resistant and reserpine-sensitive HA pools in histaminergic nerve endings. 2) Most of the neuronal HA in the brain may be located in the former pool. 3) However, the capacity of the former pool may be limited and thus most of the increased HA by L-histidine and metoprine may be transferred into the latter pool.(ABSTRACT TRUNCATED AT 250 WORDS)