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Modifying Hepatic Phospholipid Synthesis Associates with Biliary Phospholipid Secretion Rate in a Transporter-Independent Manner in Rats

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Abstract

Biliary phospholipid secretion is mediated by a multidrug resistance gene product, and its molecular subselection occurs at the site of secretion to modulates bile metastability. The aim of this study was to determine the effect of modifying hepatic phospholipid synthesis on canalicular phospholipid transporter expression and membrane fluidity. Bile-duct cannulation was performed in male Sprague-Dawley rats pretreated with or without intravenous infusion of dimethylethanolamine, an intermediate phospholipid metabolite along the pathway of phosphatidylcholine synthesis of phosphatidylethanolamine N-methylation (0.01 mg/min/100 g body wt) for 15 hr, followed by sodium taurocholate infusion (50 nmol/min/100 g body wt) with or without sulfobromophthalein (50 nmol/min/100 g body wt). Dimethylethanolamine enhanced biliary phospholipid secretion in association with a decrease in biliary phospholipid hydrophobicity. Dimethylethanolamine also increased canalicular membrane fluidity defined by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolarization, whereas the expression of multidrug resistance gene product and multidrug resistance associated protein was unchanged. In contrast, a disproportionate reduction of biliary phospholipid secretion caused by sulfobromophthalein (uncoupling) was enhanced by under the treatment with dimethylethanolamine. In conclusion, the increase in biliary phospholipid secretion and canalicular membrane fluidity without a drastic change of its canalicular transporter by dimethylethanolamine suggests that such a canalicular membrane fluidity facilitates the transporter activity and/or phospholipid molecular movement from the canalicular outer membrane into the bile. A more drastic reduction in phospholipid secretion under sulfobromophthalein-caused uncoupling indicates the possibility of a preferential distribution of relatively hydrophilic phosphatidylcholine molecules to bile salt micelles since sulfobromophthalein is known to reduce the micellar capacity to extract membrane lipids for biliary secretion.

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Authors and Affiliations

  1. First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Shigeyuki Yasumiba, Susumu Tazuma & Hidenori Ochi

  2. Onomichi General Hospital, 7-19, Kohama-cho, Onomichi, 722-8508, Japan

    Goro Kajiyama

Authors
  1. Shigeyuki Yasumiba
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  2. Susumu Tazuma
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  3. Hidenori Ochi
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  4. Goro Kajiyama
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Yasumiba, S., Tazuma, S., Ochi, H. et al. Modifying Hepatic Phospholipid Synthesis Associates with Biliary Phospholipid Secretion Rate in a Transporter-Independent Manner in Rats. Dig Dis Sci 46, 1290–1298 (2001). https://doi.org/10.1023/A:1010675615526

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