Endothelin-3 applied to the brain evokes opposite effects on bile secretion mediated by a central nitric oxide pathway.
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.
Rodríguez
Myrian R
MR
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
Sabbatini
María E
ME
Santella
Gisela
G
Dabas
Paula
P
Villagra
Alberto
A
Vatta
Marcelo S
MS
Bianciotti
Liliana G
LG
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D002779:Cholestasis / Q000139:chemically induced; D065128:Endothelin Receptor Antagonists; D019334:Endothelin-3 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D008099:Liver / Q000294:innervation / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019334:Endothelin-3; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; C087220:BQ 610; D009569:Nitric Oxide; C086539:BQ 788