Vasopressin stimulates dna synthesis in cultured rat hepatocytes

Faizullah Y. Bhora, Piyush C. Kothary, Hiroaki Imanishi, Frederic E. Eckhauser, Steven E. Raper

Research output: Contribution to journalArticle

Abstract

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague-Dawley rats were isolated using a two-step collaganase perfusion technique and plated at a density of 105/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-α (TGF-α)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-α analog). There was significant attenuation of TGF-α (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (l) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-α-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors.

Original languageEnglish (US)
Pages (from-to)706-710
Number of pages5
JournalJournal of Surgical Research
Volume57
Issue number6
DOIs
StatePublished - Dec 1994

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ASJC Scopus subject areas

  • Surgery

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