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Hypothalamic vasopressin release and hepatocyte Ca 2+ signaling during liver regeneration: an interplay stimulating liver growth and bile flow
Author(s) -
Nicou Alexandra,
Serrière Valérie,
Prigent Sylvie,
Boucherie Sylviane,
Combettes Laurent,
Guillon Gilles,
Alonso Gérard,
Tordjmann Thierry
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0082fje
Subject(s) - liver regeneration , vasopressin , hepatocyte , endocrinology , medicine , choleretic , in vivo , arginine vasopressin receptor 1b , biology , regeneration (biology) , agonist , hepatectomy , arginine vasopressin receptor 2 , receptor , microbiology and biotechnology , in vitro , biochemistry , antagonist , surgery , resection
Liver regeneration after partial hepatectomy is a plastic process during which the mechanisms that coordinate liver mass restoration compensate one another through a complex regulatory network of cytokines, growth factors, and hormones. Vasopressin, an agonist that triggers highly organized Ca 2+ signals in the liver, may be one of these factors, although little in vivo evidence is available in support of this hypothesis. We provide evidence that hypothalamic vasopressin secretion is stimulated early after partial hepatectomy. Although hepatocytes were fully responsive to vasopressin during the first hours of regeneration, they became desensitized and exhibited slow oscillating Ca 2+ responses to vasopressin on the following days. On the first day, hepatocyte V1a receptor density decreased and its lobular gradient increased in hepatectomized rats. By antagonizing the V1a receptor in vivo, we demonstrated that vasopressin contributes to NF‐κB and cyclin (D1 and A) activation, to hepatocyte progression in the cell cycle, and to liver mass restoration. Finally, vasopressin exerted a choleretic effect shortly after hepatectomy, both in the isolated perfused liver and in the intact rat. In conclusion, we provide compelling in vivo evidence that vasopressin contributes significantly to growth initiation and bile flow stimulation in the early stages of liver regeneration.