Endothelin-3 applied to the brain evokes opposite effects on bile secretion mediated by a central nitric oxide pathway

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2005-07, Vol.26 (7), p.1219-1227
• Main Authors: Rodríguez, Myrian R., Sabbatini, María E., Santella, Gisela, Dabas, Paula, Villagra, Alberto, Vatta, Marcelo S., Bianciotti, Liliana G.
• Format: Article
• Language: English
• Subjects: Animals; Bile - chemistry; Bile - secretion; Bile flow; Biological and medical sciences; Brain - drug effects; Cholestasis - chemically induced; Endothelin Receptor Antagonists; Endothelin-3 - administration & dosage; Endothelin-3 - pharmacology; Endothelin-3 - physiology; ET A receptors; ET B receptors; ET-3; Fundamental and applied biological sciences. Psychology; Liver - innervation; Liver - secretion; Nitric oxide; Nitric Oxide - metabolism; Oligopeptides - pharmacology; Piperidines - pharmacology; Portal Pressure - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Endothelin - physiology; Vagus Nerve - drug effects; Vagus Nerve - physiology; Vertebrates: endocrinology
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2005.02.003

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 ET B antagonist abolished the cholestatic effect, whereas the choleretic effect was totally inhibited by either ET A or ET B 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.