Effect of 1-Hexylcarbamoyl-5-fluorouracil (HCFU) and 1-ω-Carboxypentylcarbamoyl-5-fluorouracil (CPEFU) on Hypothalamic Neurons in the Rat

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概要

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• In order to clarify the etiology of the sensation of heat caused by 1-hexylcarbamoyl-5-fluorouracil (HCFU), a new antitumor agent, the effects of HCFU and main metabolite, 1-ω-carboxypentylcarbamoyl-5-fluorouracil (CPEFU), on single neuron activity of the rat preoptic area (POA) were studied using multibarreled electrodes.<BR>Of the 114 neurons tested, 52 were histologically localized in the POA and 62 in the other regions.Electrophoretic application of HCFU or CPEFU increased the discharge rate of POA warm sensitive neurons (which also increased in discharge rate with heat stimulation of the scrotum), and decreased the discharge rate of POA cold sensitive neurons (which also decreased with heat stimulation of the scrotum). However, both compounds non-specifically affected not only POA neurons but also neurons in other regions. In contrast to the effects of HCFU and CPEFU, electrophoretic application of sulpiride, a neuroleptic agent, inhibited spontaneous discharge of POA warm sensitive neurons and facilitated that of POA cold sensitive neurons.<BR>Although iontophoretic application of noradrenaline (NA) inhibited spontaneous discharge of POA warm sensitive neurons and facilitated that of POA cold sensitive neurons, neither acetylcholine (ACh) nor serotonin (5-HT) had any obvious affect on either activity.<BR>These findings suggest that the heat sensation induced by HCFU might be explained by its effect on the thermosensitive neurons in the POA and that this adverse effect might be relieved by treatment with sulpiride.

• 一般社団法人 日本臨床薬理学会の論文

著者

• 堀込 和利

  三井製薬工業(株)生物科学研究所創薬研究部

• 辺見 善一

  三井製薬工業株式会社生物科学研究所

• 村本 健一郎

  富山医科薬科大学第二生理学教室

• 荒木 一範

  三井製薬工業 (株) 生物科学研究所

• 佐々木 和男

  富山医科薬科大学第二生理学教室

• 辺見 善一

  三井製薬工業 (株) 生物科学研究所

• 堀込 和利

  三井製薬工業 (株) 生物科学研究所

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