Endotoxin unmasks the role of gap junctions in the liver

Paulo R A V Correa, Mateus T. Guerra, M. Fatima Leite, David C. Spray, Michael H. Nathanson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Gap junctions are thought to be necessary for proper tissue function. However, no clear hepatic phenotype has been described in patients lacking connexin 32 (Cx32), the principal gap junction in liver. To determine the physiological role of Cx32 in liver, we compared the response of wild type and Cx32-deficient mice to endotoxin, since this stress increases serum levels of hormones that bind to receptors that are asymmetrically distributed across the hepatic lobule. In hepatocyte couplets isolated from wild type mice, most hepatocytes could transfer microinjected dye to their neighbor even after treatment with endotoxin. Dye transfer was not observed in Cx32-deficient couplets. Treatment of hepatocyte couplets from wild type mice with vasopressin induced calcium (Ca 2+) waves that crossed the couplets in a concentration-dependent fashion, but the delay in transmission was markedly prolonged at all concentrations in Cx32-deficient couplets. Expression of the vasopressin receptor and the inositol 1,4,5-trisphosphate receptor was not decreased by endotoxin or in Cx32-deficient couplets. Finally, endotoxin caused transient hypoglycemia and cholestasis in wild type animals, but hypoglycemia was slightly prolonged and cholestasis was much worse in Cx32-deficient mice treated with endotoxin. The hepatic response to endotoxin is markedly impaired in the absence of Cx32. Thus, an important role of gap junctions in the liver is to assure integrated and uniform tissue response in times of stress.

Original languageEnglish (US)
Pages (from-to)718-726
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume322
Issue number3
DOIs
StatePublished - Sep 24 2004

Fingerprint

Gap Junctions
Endotoxins
Liver
Hepatocytes
Cholestasis
Hypoglycemia
Coloring Agents
Tissue
Inositol 1,4,5-Trisphosphate Receptors
Vasopressin Receptors
Wild Animals
connexin 32
Inositol
Vasopressins
Animals
Hormones
Calcium
Phenotype
Therapeutics
Serum

Keywords

  • Calcium
  • Connexin 32
  • Inositol 1,4,5-trisphosphate receptor and endotoxin
  • Liver

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Endotoxin unmasks the role of gap junctions in the liver. / Correa, Paulo R A V; Guerra, Mateus T.; Leite, M. Fatima; Spray, David C.; Nathanson, Michael H.

In: Biochemical and Biophysical Research Communications, Vol. 322, No. 3, 24.09.2004, p. 718-726.

Research output: Contribution to journalArticle

Correa, Paulo R A V ; Guerra, Mateus T. ; Leite, M. Fatima ; Spray, David C. ; Nathanson, Michael H. / Endotoxin unmasks the role of gap junctions in the liver. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 322, No. 3. pp. 718-726.
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