Franchini L F, Rubinstein M, Vivas L
Instituto de Investigación Médica Mercedes y Martín Ferreyra, Casilla de Correo 389, 5000 Córdoba, Argentina.
Neuroscience. 2003;121(4):875-81. doi: 10.1016/s0306-4522(03)00485-8.
Central opioid and oxytocinergic systems have been involved in the regulatory control of sodium appetite. In addition, previous studies support the existence of a functional interaction between opioid peptides and oxytocinergic pathways, and suggest that beta-endorphin neurons would modulate the activity of central oxytocinergic pathways, its pituitary secretion and sodium appetite. To investigate the role of this opioid peptide in the control of oxytocin (OT) synthesis and sodium appetite regulation we used mice with gene dosage-dependent variations in brain beta-endorphin content, expressing either 100%, 50%, or 0% of normal beta-endorphin content. Our results show that beta-endorphin knockout (KO) and heterozygous (HT) mutant mice consume approximately a 50% less 2% NaCl solution compared with wild type mice (WT), after furosemide and low sodium diet treatment. These data suggest that beta-endorphin may facilitate induced sodium appetite, giving new evidence about the role of beta-endorphin on sodium appetite behavior. Our data also indicate that OT mRNA levels evaluated by in situ hybridization significantly increased within the hypothalamic paraventricular nucleus of WT animals after induced sodium ingestion, giving support to former evidence indicating an inhibitory role for central OT in the control of sodium appetite. Moreover, beta-endorphin mutated mice have similar higher levels of OT mRNA expression after the different conditions analyzed: basal, control or experimental, compared with WT mice. Both control HT and KO mice showed higher OT mRNA expression levels than control WT group and these levels did not change after induced sodium intake. Taken together, our data suggest that the reduced sodium ingestion observed in beta-endorphin deficient mice could be due to a higher expression of the OT gene. This conclusion would support the hypothesis that OT inhibits sodium intake and provides new evidence about beta-endorphin modulation of OT synthesis and sodium appetite.
中枢阿片类和催产素能系统参与了钠食欲的调节控制。此外，先前的研究支持阿片肽与催产素能通路之间存在功能相互作用，并表明β-内啡肽神经元会调节中枢催产素能通路的活性、其垂体分泌以及钠食欲。为了研究这种阿片肽在催产素（OT）合成控制和钠食欲调节中的作用，我们使用了脑β-内啡肽含量存在基因剂量依赖性变化的小鼠，其β-内啡肽含量分别为正常含量的100%、50%或0%。我们的结果表明，在速尿和低钠饮食处理后，β-内啡肽基因敲除（KO）和杂合（HT）突变小鼠与野生型小鼠（WT）相比，摄入的2% NaCl溶液减少了约50%。这些数据表明β-内啡肽可能促进诱导性钠食欲，为β-内啡肽在钠食欲行为中的作用提供了新证据。我们的数据还表明，诱导钠摄入后，通过原位杂交评估的WT动物下丘脑室旁核内OT mRNA水平显著增加，这支持了先前的证据，即中枢OT在钠食欲控制中起抑制作用。此外，与WT小鼠相比，β-内啡肽突变小鼠在分析的不同条件下（基础、对照或实验），OT mRNA表达水平也有类似的升高。对照HT和KO小鼠的OT mRNA表达水平均高于对照WT组，且这些水平在诱导钠摄入后没有变化。综上所述，我们的数据表明，在β-内啡肽缺乏的小鼠中观察到的钠摄入量减少可能是由于OT基因的更高表达。这一结论将支持OT抑制钠摄入的假说，并为β-内啡肽对OT合成和钠食欲的调节提供新证据。
