Effect of insulin, dexamethasone, and glucagon on the amino acid transport ability of four rat hepatoma cell lines and rat hepatocytes in culture.

The basal level and hormone-affectedaminoacidtrans portof rat hepatocytesand rat hepatomacell lines H4-bI E-C3 (H35), HTC, McA-RH8994 (8994), and McA-RH7777 (7777) in culture were examined by investigating the amount of a-[1-14C]-aminoisobutyricacid (AIB) trans ported in 4 mm and up to 4 hr at 37°. The substances testedwere insulin,dexamethasone(DEX),glucagon,and dibutyryl cyclic adenosine 3' :5-monophosphate. Without any hormonetreatmentcell line 7777exhibitedthe maxi mum rate of AIB uptake, followed in order by cell lines HTC, 8994, H35, and hepatocytes. Insulin increasedthe uptakeof AIB by hepatocytesas well as by all fourof the hepatomacell lines. DEX increasedAIB transportin cell lines H-35 and 8994 and inhibitedit in hepatocytesand hepatomacell lines HTC and 7777. The effect of insulin and DEXwas additivein cell lines H35and 8994and was antagonistic in hepatocytes and cell lines HTC and 7777. In contrastto their stimulatoryeffect on AIB transportin rat liver parenchymabcells, glucagonor dibutyrylcyclic adenosine 3':5'-monophosphatehad no effect on the transportsystemof any of these four cell lines. Further more, the potentiationof AIB transport by DEX, in re sponse to glucagonor dibutyrybcyclic adenosine 3':5'monophosphateas seen in rat liver parenchymalcells, couldnotbe observedin anyof these fourcell lines. Both actinomycin D and cycboheximideblocked any of the effects of insulin, DEX, or glucagon in all of these cell culturetypes.Onthe basisof these findings,we conclude that in spite of several similarities there is a marked heterogeneityin hormoneresponsesamongthe various hepatoma cell lines, althougheach differs in some re spectfromthe hepatocytes.