O'Shea R D, Gundlach A L
University of Melbourne Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Peptides. 1995;16(6):1117-25. doi: 10.1016/0196-9781(95)00075-u.
The role of neuropeptide Y (NPY) in the central control of appetite and energy balance is now established, but its involvement in the control of drinking and fluid homeostasis is less well characterized. Central administration of NPY stimulates drinking in rats, an effect believed to be independent of its orexigenic effects. Recent studies have demonstrated increased preproneuropeptide Y (preproNPY) mRNA in the arcuate nucleus (ARC) of the rat following food deprivation (FD) or water deprivation (WD). Because WD also suppresses food intake, it was not clear whether the osmotic or the anorectic effects of this stimulus were responsible for increased ARC preproNPY mRNA. In an attempt to distinguish between these possibilities, the present study further examined the effects of hyperosmotic stimuli on preproNPY mRNA in the ARC. Salt loading (4 or 7 days) and WD (4 days) both increased the abundance of preproNPY mRNA in the ARC. These increases were proportional to the severity and duration of treatment and were related to the degree of anorexia and weight loss. In a separate study WD, FD, or combined food and water deprivation (4 days) all produced similar decreases in body weight, but WD produced a smaller increase in ARC preproNPY mRNA. All of these treatments resulted in the appearance of NPY-like immunoreactivity in ARC neuronal perikarya. Together these findings suggest that NPY neuron activity in the ARC may be regulated by decreases in food intake rather than changes in body weight per se or increased osmolarity and support other data implicating NPY in the central regulation of energy homeostasis.
神经肽Y(NPY)在食欲和能量平衡的中枢控制中的作用现已明确,但其在饮水控制和液体稳态中的作用则了解较少。向大鼠中枢给予NPY会刺激其饮水,这一效应被认为与其促食欲作用无关。最近的研究表明,在食物剥夺(FD)或水剥夺(WD)后,大鼠弓状核(ARC)中前神经肽Y原(preproNPY)mRNA水平升高。由于WD也会抑制食物摄入,因此尚不清楚这种刺激的渗透作用还是厌食作用导致了ARC中前神经肽Y原mRNA水平升高。为了区分这些可能性,本研究进一步考察了高渗刺激对ARC中前神经肽Y原mRNA的影响。盐负荷(4天或7天)和WD(4天)均增加了ARC中前神经肽Y原mRNA的丰度。这些增加与治疗的严重程度和持续时间成正比,且与厌食和体重减轻的程度相关。在另一项研究中,WD、FD或食物和水联合剥夺(4天)均使体重出现相似程度的下降,但WD使ARC中前神经肽Y原mRNA的增加幅度较小。所有这些处理均导致ARC神经元胞体中出现NPY样免疫反应性。这些发现共同表明,ARC中NPY神经元的活性可能受食物摄入量减少的调节,而非体重本身的变化或渗透压升高的影响,这也支持了其他表明NPY参与能量稳态中枢调节的数据。