Hypothalamic neuronal histamine is involved in the central regulation of energy expenditure through the activation of sympathetic nerves innervating brown adipose tissue (BAT). The present study examined the effect of L-histidine, a precursor of neuronal histamine, on BAT sympathetic nerve activity in rats. Infusion of histamine at a dose of 1 nmol/rat into the third cerebroventricle significantly increased BAT sympathetic nerve activity as compared with the effect of phosphate buffered saline (P < 0.05). Intraperitoneal (i.p.) injection of L-histidine (0.3 mmol/rat) also significantly increased BAT sympathetic nerve activity as compared with the effect of PBS (P < 0.05). Pretreatment with an i.p. bolus injection of 224 micromol/kg alpha-fluoromethylhistidine, a suicide inhibitor of the histamine synthesizing enzyme histidine decarboxylase, blocked the stimulatory effect of l-histidine on BAT sympathetic nerve activity. These results indicate that L-histidine regulates BAT sympathetic nerve activity through its conversion into neuronal histamine in the hypothalamus.
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