Regulation of cytochrome P-450p by phenobarbital and phenobarbital-like inducers in adult rat hepatocytes in primary monolayer culture and in vivo

Biochemistry ◽  
1986 ◽  
Vol 25 (5) ◽  
pp. 1124-1133 ◽  
Author(s):  
Erin G. Schuetz ◽  
Steven A. Wrighton ◽  
Stephen H. Safe ◽  
Philip S. Guzelian
1984 ◽  
Vol 144 (3) ◽  
pp. 245-256
Author(s):  
TSUGUHIKO NAKAI ◽  
YASUNORI KUTSUMI ◽  
YOSHIKAZU SAKAMOTO ◽  
KOJI OIDA ◽  
SUSUMU MIYABO ◽  
...  

1981 ◽  
Vol 2 (5) ◽  
pp. 491-500
Author(s):  
SHIRO YAMADA ◽  
TSUGUHIKO NAKAI ◽  
YASUNORI KUTSUMI ◽  
RYOYU TAKEDA ◽  
KYUICHI KURAKANE ◽  
...  

1977 ◽  
Vol 72 (6) ◽  
pp. 1232-1239 ◽  
Author(s):  
Philip S. Guzelian ◽  
D. Montgomery Bissell ◽  
Urs A. Meyer

1979 ◽  
Vol 73 (3) ◽  
pp. 369-383 ◽  
Author(s):  
F Ismail-Beigi ◽  
D M Bissell ◽  
I S Edelman

We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate.


1983 ◽  
Vol 244 (1) ◽  
pp. C17-C23 ◽  
Author(s):  
R. Wondergem

Rat hepatocytes in primary monolayer culture demonstrated two stable states of transmembrane potential (Em). Low potentials ranging from -10 to -15 mV followed impalements with glass microelectrodes, and in some cells low potentials increased spontaneously or in response to a train of intermittent current (5 nA) to stable potentials of -50 mV, which were comparable to hepatocyte Em in vivo. Adding insulin at 20 mU/ml depolarized the stable higher Em 22.4 +/- 2.6 mV (n = 6) over an 11-min interval, and input resistance increased 21.4 +/- 4.7 M omega (n = 6) during the depolarization. The insulin effect was dose dependent, because adding insulin at 0.2 mU/ml depolarized the stable high Em 5.0 +/- 1.5 mV (n = 3) and increased input resistance 6.3 +/- 1.8 M omega (n = 3). In one experiment the Em repolarized 32 min after insulin was washed out. Adding metabolic inhibitors KCN (1 mM) and 2,4-dinitrophenol (10 and 1 mM) and increasing external potassium (60 mM, with external sodium reduced equivalently) also depolarized Em, but they did not increase input resistance. Thus insulin depolarized hepatocytes from a stable high Em, which is equivalent to the Em of liver in vivo, to a stable low Em, which occurs in hepatocytes in primary monolayer culture. This hormone action is consistent with changes in membrane ion conductance, and it further demonstrates that these cells can sustain two stable states of Em.


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