IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Endothelins induce choleresis through ETB receptors coupled to nitric oxide release and vago-vagal reflexes
Autor/es:
MYRIAN R. RODRIGUEZ; MARIA S. VENTIMIGLIA; ANA C. NAJENSON; MARCELO S. VATTA; LILIANA G. BIANCIOTTI
Reunión:
Congreso; Experimental Biology'12; 2012
Resumen:
We previously showed that brain applied ET-1 and ET-3 in rats induce choleresis or cholestasis depending on the dose. In this study we evaluated if endothelins (ETs) regulated bile secretion when peripherally infused. Animals were prepared with jugular vein and bile duct cannulation to infuse drugs and collect bile samples. At the doses used ETs did not affect hepatic blood flow or portal venous pressure. ETs induced significant choleresis, being ET-1 more potent than ET-3. ETs increased bile salts, electrolytes and glutathione excretion supporting enhanced bile acid dependent and independent flows. ETs-induced choleresis was mediated by ETB receptors coupled to nitric oxide and abolished by truncal vagotomy or capsaicin perivagal application. RT-PCR and western blot analysis showed ETA and ETB receptor expression in the vagus nerve. ETs through ETB stimulated sodium taurocholate co transporter polypeptide (Ntcp) and aquaporin 8 (AQP8) translocation to the plasma membrane and augmented Ntcp, AQP8, bile salt export pump (Bsep) and multidrug resistance protein 2 (Mrp2) in microsomal membranes. Real time PCR studies showed that exposure to ETs increased the mRNAs of these transporters. ETs induced choleresis through ETB receptors coupled to nitric oxide and vago-vagal reflexes without involving hemodynamic changes. These findings suggest that ETs may play a beneficial role when bile secretion is impaired.