Rodríguez Myrian R, Sabbatini María E, Santella Gisela, Dabas Paula, Villagra Alberto, Vatta Marcelo S, Bianciotti Liliana G
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
Peptides. 2005 Jul;26(7):1219-27. doi: 10.1016/j.peptides.2005.02.003. Epub 2005 Feb 26.
We sought to establish Endothelin (ET-3) role in the central regulation of bile secretion in the rat. The intracerebroventricular (icv) injection of ET-3 evoked a cholestatic or a choleretic effect depending on the administered dose. Lower doses increased bile flow and bicarbonate excretion, whereas higher doses decreased bile flow and bile acid output. ET-3 effects were dependent on brain nitric oxide and independent of the autonomic nervous system or hemodynamic variations. A selective ETB antagonist abolished the cholestatic effect, whereas the choleretic effect was totally inhibited by either ETA or ETB selective blockade. These results show that ET-3 applied to the brain modified through a nitric oxide pathway distinct bile flow fractions depending on the administered dose and give further insights into the complexity of brain-liver interaction.
我们试图确定内皮素（ET-3）在大鼠胆汁分泌中枢调节中的作用。脑室内（icv）注射ET-3会根据给药剂量引起胆汁淤积或利胆作用。较低剂量可增加胆汁流量和碳酸氢盐排泄，而较高剂量则会降低胆汁流量和胆汁酸输出。ET-3的作用依赖于脑内一氧化氮，且与自主神经系统或血流动力学变化无关。选择性ETB拮抗剂可消除胆汁淤积作用，而ETA或ETB选择性阻断则可完全抑制利胆作用。这些结果表明，脑内应用的ET-3通过一氧化氮途径根据给药剂量改变不同的胆汁流量分数，并进一步揭示了脑-肝相互作用的复杂性。
