Fukagawa K, Sakata T, Shiraishi T, Yoshimatsu H, Fujimoto K, Ookuma K, Wada H
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Japan.
Am J Physiol. 1989 Mar;256(3 Pt 2):R605-11. doi: 10.1152/ajpregu.1989.256.3.R605.
To clarify the physiological role of hypothalamic neuronal histamine in control of food intake, ingestive behavior and neuronal activity were investigated under blockade or diurnal fluctuation of hypothalamic neuronal histamine. Histamine H1- but not H2-receptor antagonist potently induced feeding in a dose-related manner after infusion into rat third cerebroventricle at 1100 h. Elicitation was attenuated after infusion at 1940 h when histamine content in the hypothalamus was low and was abolished after intraperitoneal pretreatment with 0.11 mmol alpha-fluoromethylhistidine (alpha-FMH), a specific suicide inhibitor of histidine decarboxylase. Electrophoretic application of a histamine H1-receptor antagonist to ventromedial hypothalamic neurons specifically suppressed activities of glucose-responding neurons that are related to food intake. The suppressive effect was also attenuated by intraperitoneal pretreatment with alpha-FMH. These results suggest that feeding induced by histamine H1-receptor antagonists is due to blockade of neuronal histamine at the site of histamine H1-receptors, at least in part, in the ventromedial hypothalamus and that diurnal fluctuation of feeding behavior may reflect circadian variation of neuronal histamine level.
为阐明下丘脑神经元组胺在食物摄入控制中的生理作用，在阻断下丘脑神经元组胺或其昼夜波动的情况下，对摄食行为和神经元活动进行了研究。组胺H1受体拮抗剂而非H2受体拮抗剂，于11:00注入大鼠第三脑室后，以剂量相关方式强力诱导进食。19:40注入后，诱导作用减弱，此时下丘脑组胺含量较低，且在用0.11 mmolα-氟甲基组胺（α-FMH，组氨酸脱羧酶的特异性自杀抑制剂）进行腹腔预处理后，诱导作用消失。将组胺H1受体拮抗剂电泳施加于腹内侧下丘脑神经元，可特异性抑制与食物摄入相关的葡萄糖反应神经元的活动。腹腔注射α-FMH预处理也可减弱这种抑制作用。这些结果表明，组胺H1受体拮抗剂诱导的进食至少部分是由于组胺在腹内侧下丘脑的组胺H1受体部位被阻断，且进食行为的昼夜波动可能反映了神经元组胺水平的昼夜变化。
