Galbraith R A, Kow L M, Pfaff D, Kappas A
Rockefeller University Hospital, New York, New York 10021.
Am J Physiol. 1992 Oct;263(4 Pt 2):R805-12. doi: 10.1152/ajpregu.1992.263.4.R805.
Intracerebroventricular administration of small amounts (0.1 mumol/kg body wt) of cobalt protoporphyrin (CoPP), a synthetic analogue of heme, results in transient hypophagia and prolonged reduction in body weight of rats. Statistically significant hypophagia is detectable within 3 h of CoPP infusion. These changes are accompanied by prompt and sustained reductions in running wheel revolutions, a measure of spontaneous locomotor activity. Bilateral intrahypothalamic injections of CoPP at far lower doses (4 nmol/rat) resulted in similar findings following infusion into the paraventricular, dorsomedial, and ventromedial nuclei, but the compound had no such effect when injected into the thalamus or the lateral hypothalamic area. These effects were also observed following microinjection of the natural metalloporphyrin, heme, into the medial hypothalamic nuclei. Inorganic cobalt, iron, protoporphyrin, and magnesium protoporphyrin injected similarly were without such effect. These findings provide further evidence that the site of the previously described actions of CoPP in reducing food intake and body weight in rats resides, at least in part, in the medial hypothalamus. Furthermore, this study expands the spectrum of metalloporphyrins that act in the central nervous system to elicit these changes from synthetic compounds such as CoPP to heme, the natural, physiological metalloporphyrin.
脑室内注射少量（0.1微摩尔/千克体重）的钴原卟啉（CoPP），一种血红素的合成类似物，会导致大鼠出现短暂的摄食减少以及体重的长期下降。在CoPP输注后3小时内可检测到具有统计学意义的摄食减少。这些变化伴随着跑步轮转动次数的迅速且持续减少，跑步轮转动次数是自发运动活动的一种衡量指标。以低得多的剂量（4纳摩尔/大鼠）双侧下丘脑内注射CoPP，在注入室旁核、背内侧核和腹内侧核后会产生类似的结果，但该化合物注入丘脑或下丘脑外侧区时则没有这种作用。在将天然金属卟啉血红素微量注射到下丘脑内侧核后也观察到了这些效应。同样注射的无机钴、铁、原卟啉和镁原卟啉则没有这种作用。这些发现进一步证明，先前描述的CoPP在降低大鼠食物摄入量和体重方面的作用部位至少部分位于下丘脑内侧。此外，本研究扩展了在中枢神经系统中发挥作用以引发这些变化的金属卟啉的范围，从CoPP等合成化合物扩展到了天然的生理性金属卟啉血红素。
