Liu Y, Ganguly T, Hyde J F, Vore M
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536.
Am J Physiol. 1995 Jan;268(1 Pt 1):G11-7. doi: 10.1152/ajpgi.1995.268.1.G11.
We have shown that prolactin (Prl) increases the transhepatic transport of taurocholate (TC) in postpartum rats and following treatment of ovariectomized (Ovx) rats with ovine Prl (oPrl). The present studies were designed to determine if treatment of Ovx rats with oPrl (100, 300, or 600 micrograms/day, 7 days iv) 1) increases Na(+)-TC cotransport in basolateral plasma membrane vesicles (bLPM), 2) induces a corresponding increase in the steady-state levels of Na(+)-TC cotransport polypeptide (Ntcp mRNA), and 3) if the oPrl-mediated increase in Na(+)-TC cotransport activity is blocked by cycloheximide, an inhibitor of protein synthesis. oPrl (300 micrograms/day) induced a twofold increase in the maximal velocity for Na(+)-TC cotransport in both hepatocytes and bLPM vesicles with little change in the Michaelis constant. Infusion of oPrl at a dose of 100, 300, or 600 micrograms/day increased steady-state Ntcp mRNA four-, ten-, and twofold, respectively. Finally, cycloheximide blocked the oPrl-mediated increase in Na(+)-TC cotransport but did not affect basal activity. These data support the hypothesis that an increase in Ntcp mRNA followed by increased synthesis and incorporation of Ntcp in the plasma membrane is responsible for the oPrl-mediated increase in Na(+)-TC cotransport in the basolateral plasma membrane domain of the hepatocyte.
我们已经表明，催乳素（Prl）可增加产后大鼠以及用绵羊催乳素（oPrl）处理去卵巢（Ovx）大鼠后牛磺胆酸盐（TC）的经肝转运。本研究旨在确定用oPrl（100、300或600微克/天，静脉注射7天）处理Ovx大鼠是否：1）增加基底外侧质膜囊泡（bLPM）中Na(+)-TC共转运；2）诱导Na(+)-TC共转运多肽（Ntcp mRNA）的稳态水平相应增加；3）蛋白合成抑制剂环己酰亚胺是否会阻断oPrl介导的Na(+)-TC共转运活性增加。oPrl（300微克/天）使肝细胞和bLPM囊泡中Na(+)-TC共转运的最大速度增加了两倍，而米氏常数变化不大。以100、300或600微克/天的剂量输注oPrl分别使稳态Ntcp mRNA增加了四倍、十倍和两倍。最后，环己酰亚胺阻断了oPrl介导的Na(+)-TC共转运增加，但不影响基础活性。这些数据支持以下假设：Ntcp mRNA增加，随后Ntcp在质膜中的合成和整合增加，是oPrl介导的肝细胞基底外侧质膜结构域中Na(+)-TC共转运增加的原因。
