Morris M J, Pavia J M
Department of Pharmacology, University of Melbourne, Victoria, Australia.
J Neurochem. 1998 Oct;71(4):1519-24. doi: 10.1046/j.1471-4159.1998.71041519.x.
Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) are present at high concentrations in the hypothalamus where they mediate important endocrine and autonomic functions. Morphological and physiological studies have suggested an interaction between these peptides, and opposing actions of CRF and NPY have been reported on feeding and other behaviors. This study investigated the effect of CRF on NPY release in vivo, measured by push-pull techniques, in the anesthetized rat. Push-pull probes implanted into the paraventricular nucleus of the hypothalamus (PVN) were perfused with modified Ringer solution containing bovine serum albumin at 15 microl/min, and the perfusate was lyophilized prior to NPY radioimmunoassay. NPY overflow from the rat PVN was increased threefold by perfusion of a depolarizing concentration of potassium (50 mmol/L KCl). When CRF was administered into the PVN via the push-pull cannula at 1 or 5 microg/ml, dose-dependent increases in NPY overflow of two- and fivefold were observed (p < 0.05). These increases were abolished by prior intracerebroventricular (i.c.v.) administration of the CRF antagonist [D-Phe12,Nle(21,38),C(alpha)MeLeu32]CRF (12-41) at 1 or 5 microg/microl, respectively. NPY overflow returned promptly to resting levels following CRF administration. In contrast, when CRF was administered by i.c.v. bolus at a similar total dose (2 microg), no significant effect on NPY overflow was observed. These data provide in vivo evidence for an interaction between CRF and NPY at the level of the PVN.
神经肽Y（NPY）和促肾上腺皮质激素释放因子（CRF）在下丘脑中以高浓度存在，它们在那里介导重要的内分泌和自主功能。形态学和生理学研究表明这些肽之间存在相互作用，并且已经报道了CRF和NPY在进食及其他行为上的相反作用。本研究通过推挽技术，在麻醉大鼠体内研究了CRF对NPY释放的影响。将植入下丘脑室旁核（PVN）的推挽探针以15微升/分钟的速度用含有牛血清白蛋白的改良林格溶液灌注，灌注液在进行NPY放射免疫测定之前进行冻干。通过灌注去极化浓度的钾（50 mmol/L KCl），大鼠PVN的NPY溢出增加了三倍。当通过推挽套管以1或5微克/毫升的浓度将CRF注入PVN时，观察到NPY溢出呈剂量依赖性增加，分别增加了两倍和五倍（p < 0.05）。这些增加分别被预先脑室内（i.c.v.）给予1或5微克/微升的CRF拮抗剂[D-Phe12，Nle(21,38)，C(α)MeLeu32]CRF（12-41）所消除。给予CRF后，NPY溢出迅速恢复到静息水平。相比之下，当以相似的总剂量（2微克）通过i.c.v.推注给予CRF时，未观察到对NPY溢出有显著影响。这些数据为PVN水平上CRF和NPY之间的相互作用提供了体内证据。
