Erickson J C, Clegg K E, Palmiter R D
Howard Hughes Institute, University of Washington, Seattle, USA.
Nature. 1996 May 30;381(6581):415-21. doi: 10.1038/381415a0.
Neuropeptide Y (NPY), a 36-amino-acid transmitter distributed throughout the nervous system, is thought to function as a central stimulator of feeding behaviour. NPY has also been implicated in the modulation of mood, cerebrocortical excitability, hypothalamic-pituitary signalling, cardiovascular physiology and sympathetic function. However, the biological significance of NPY has been difficult to establish owing to a lack of pharmacological antagonists. We report here that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation. Mutant mice decrease their food intake and lose weight, initially to a greater extent than controls, when treated with recombinant leptin. Occasional, mild seizures occur in NPY-deficient mice and mutants are more susceptible to seizures induced by a GABA (gamma-aminobutyric acid) antagonist. These results indicate that NPY is not essential for certain feeding responses or leptin actions but is an important modulator of excitability in the central nervous system.
神经肽Y（NPY）是一种由36个氨基酸组成的递质，分布于整个神经系统，被认为是进食行为的中枢刺激物。NPY还与情绪调节、大脑皮质兴奋性、下丘脑 - 垂体信号传导、心血管生理和交感神经功能有关。然而，由于缺乏药理学拮抗剂，NPY的生物学意义一直难以确定。我们在此报告，缺乏NPY的小鼠食物摄入量和体重正常，在食物剥夺后会变得食欲亢进。用重组瘦素治疗时，突变小鼠的食物摄入量减少并体重减轻，最初比对照组更明显。NPY缺陷小鼠偶尔会出现轻度癫痫发作，并且突变体对γ-氨基丁酸（GABA）拮抗剂诱导的癫痫发作更敏感。这些结果表明，NPY对于某些进食反应或瘦素作用并非必不可少，但它是中枢神经系统兴奋性的重要调节剂。
