THE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR (IGFR) IS INVOLVED IN ESTRADIOL-17BETA-DGLUCURONIDE (E17G) INDUCED CHOLESTASIS IN ISOLATED PERFUSED RAT LIVER (IPRL).

BAROSSO, ISMAEL R.; ANDERMATTEN, ROMINA B; CIRIACI, NADIA; BAROSSO ISMAEL; MAIDAGÁN, P M; SANCHEZ POZZI, ENRIQUE J.

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC

E17G internalizes canalicular transporters such as Mrp2 and$sep model of intrahepatic cholestasis of pregnancy, by activatingtYo different pathYays each one involving an estrogenreceptor: ERα or )24. )24 activates adenylyl cyclase2-Aand 2+-/AMt, being the latter pathYay responsible for Meepingtransporters in a subapical space, restraining reinsertion. PreviousYorMs demonstrated that +)F4 participates doYnstream of)24 in culture of rat hepatocyte couplets, so the role of +)F4Yas evaluated in a physiological model as +24L.Livers Yere perfused in situ via the portal vein in a nonrecirculatingsinglepass design. Taurocholate z/, $sep sustrate and chloro,dinitrobenzene . z/, precursor of &02glutathione,/rp substrate Yere added to the perfusion medium to estimate$sep and /rp activities. After a min. equilibration period,Tyrphostin A) A), n/, +)F4 inhibitor, or its solvent&/S1, zl/L Yas added to the reservoir. Ten minutes later, a min basal bile sample Yas collected, folloYed by administrationof E) zmol/liver, intraportal or its solvent &/S1/ $SAin saline, and bile collected at min intervals for min. bile floYYas determined gravimetrically only if initial bile floY Yas greaterthan zL/ min/Mg. $iliary excretion of &02glutathione Yasdetermined by H2LC and that of $S by ahydroxysteroid method.A) did not prevent the drop induced by E) in thethree parameters measured, but accelerated the recovery of bothbile floY significant from min of E) administration on andbiliary excretion of &02glutathione and $S significant from min of E) administration on. p., n. A similar behaviorYas previously observed Yith inhibitors of 2+-, a protein thatallegedly participates in the same pathYay of +)F4.Conclusion these results confirm the role of +)F4 in estrogencholestasis, Yhich expands the potential therapeutic targets forits treatment.