INVOLVEMENT OF CORTICOTROPIN RELEASING-FACTOR (CRF) IN THE THERMOGENIC AND ANOREXIC ACTIONS OF SEROTONIN (5-HT) AND RELATED-COMPOUNDS
INVOLVEMENT OF CORTICOTROPIN RELEASING-FACTOR (CRF) IN THE THERMOGENIC AND ANOREXIC ACTIONS OF SEROTONIN (5-HT) AND RELATED-COMPOUNDS
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DOI：
10.1016/0006-8993(91)90348-y
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发表时间：
1991-08-02
期刊：
影响因子：
2.9
通讯作者：
ROTHWELL, NJ
中科院分区：
文献类型：
--
作者：
LEFEUVRE, RA;AISENTHAL, L;ROTHWELL, NJ
本研究探讨了促肾上腺皮质激素释放因子（CRF）参与5-羟色胺（5-HT）的生热和增敏作用。将血清素能化合物和CRF抗体直接注射到清醒的雄性Sprague-Dawley大鼠的第三脑室中。通过间接量热法测量全身耗氧量的变化来测量产热。5-HT（0.5-50 μ g，i.c.v.）显著增加静息耗氧量（V（O2）;最大增加12.5%），对行为无明显影响。在中心注射5-HT前体色氨酸（14 μ g，i. c. v.）或5-羟色氨酸（5-HTP，20 μ g，i. c. v.），和外周（10 mg/kg，腹腔注射）或中心（30 μ g，i. c. v.）注射5-HT再摄取抑制剂DL-芬氟拉明。施用多克隆CRF抗体（3 μ l，i. c. v.）10分钟前，显著降低（77-106%）的V（O2）的增加，观察到响应于5-HTP（20 μ g），5-HT（50 μ g）或芬氟拉明外周注射，但不是响应于30 μ g芬氟拉明（i. c. v.）或20 μ g 5-HT。自愿的食物摄入量测定6小时后，大鼠饥饿16小时。在中枢注射5-HT或5-HTP，以及中枢或外周注射芬氟拉明的大鼠中，6小时摄食量显著减少（30-60%）。用CRF抗体预处理显著减弱（30-70%）在响应于5-HT（40 μ g）、5-HTP（40 μ g）和芬氟拉明（30和50 μ g）的中枢注射中观察到的食物摄入的减少，但在20 μ g 5-HTP、20 μ g 5-HT或芬氟拉明（10 mg/kg）的外周注射后观察不到。5-羟色胺及其相关化合物的中枢产热和促热作用似乎至少部分由CRF介导。
The present study investigated the involvement of corticotrophin-releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) in the rat. Serotonergic compounds and CRF antibody were injected directly into the third ventricle of conscious, male Sprague-Dawley rats. Thermogenesis was measured as changes in whole body oxygen consumption by indirect calorimetry. Central injections of 5-HT (0.5-50-mu-g, i.c.v.) significantly increased resting oxygen consumption (V(O2); maximum 12.5% increase), without obvious effects on behaviour. Similar increases in V(O2) (12-17%) were observed following central injections of the 5-HT precursors, tryptophan (14-mu-g, i.c.v.) or 5-hydroxytryptophan (5-HTP, 20-mu-g, i.c.v.), and peripheral (10 mg/kg, i.p.) or central (30-mu-g, i.c.v.) injections of the 5-HT reuptake inhibitor, DL-fenfluramine. Administration of a polyclonal CRF antibody (3-mu-l, i.c.v.) 10 min prior to serotonergic compounds, significantly reduced (77-106%) the increases in V(O2) observed in response to central injections of 5-HTP (20-mu-g), 5-HT (50-mu-g) or peripheral injections of fenfluramine, but not those observed in response to either 30-mu-g fenfluramine (i.c.v.) or 20-mu-g 5-HT. Voluntary food intake was measured for 6 h in rats following 16 h starvation. Six-hour food intake was significantly reduced (30-60%) in rats given central injections of 5-HT or 5-HTP, and central or peripheral injections of fenfluramine. Pretreatment with CRF antibody significantly attenuated (30-70%) the reductions in food intake observed in response to central injection of 5-HT (40-mu-g), 5-HTP (40-mu-g) and fenfluramine (30 and 50-mu-g), but not those observed after either 20-mu-g 5-HTP, 20-mu-g 5-HT or peripheral injection of fenfluramine (10 mg/kg). The central thermogenic and anorexic actions of serotonin and related compounds appear to be mediated, at least in part, by CRF.