Turner M B, Corp E S, Galbraith R A
Duke University Medical College, Durham, NC 27710.
Physiol Behav. 1994 Nov;56(5):1009-14. doi: 10.1016/0031-9384(94)90336-0.
The administration of cobalt protoporphyrin results in transient decreases in food intake and prolonged weight loss in rats. After IVC injection of cobalt protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated control rats within 48 h. At the same time, the concentrations of mRNA for neuropeptide Y increase approximately twofold in the hypothalamus. The failure of these animals to display a feedings response to elevation of endogenous NPY concentration is mimicked by their failure to respond to exogenous. ICV injections of neuropeptide Y. Because NPY binding studies are confounded by high nonspecific binding, radiolabeled PYY was used to measure binding to hypothalamic membranes and for autoradiography with hypothalamic sections. No abnormalities in the number of receptors or the affinity of the binding interaction were noted. In addition, hypothalamic concentrations of cyclic AMP were unchanged following treatment with either cobalt protoporphyrin or NPY. These results indicate that the locus of the failure of CoPP-treated animals to feed after administration of NPY must be either distal to, or unrelated to, the NPY receptor in the hypothalamus.
给予大鼠钴原卟啉会导致其食物摄入量短暂减少，并出现长期体重减轻。静脉注射钴原卟啉后，在48小时内，接受治疗的大鼠的食物摄入量降至接受载体治疗的对照大鼠的10%。与此同时，下丘脑神经肽Y的mRNA浓度增加约两倍。这些动物对内源性神经肽Y浓度升高未表现出进食反应，这与它们对外源性神经肽Y无反应相似。脑室内注射神经肽Y。由于神经肽Y结合研究受到高非特异性结合的干扰，因此使用放射性标记的肽YY来测量与下丘脑膜的结合，并用于下丘脑切片的放射自显影。未发现受体数量或结合相互作用亲和力存在异常。此外，用钴原卟啉或神经肽Y处理后，下丘脑环磷酸腺苷的浓度没有变化。这些结果表明，钴原卟啉处理的动物在给予神经肽Y后无法进食的部位必定位于下丘脑神经肽Y受体的远端或与之无关。
