Gap junctional communication coordinates vasopressin-induced glycogenolysis in rat hepatocytes.
Because hepatocytes communicate via gap junctions, it has been proposed that Ca2+ waves propagate through this pathway and in the process activate Ca2+-dependent cellular responses. We testedthis hypothesis by measuring vasopressin-induced glycogenolysis in short-term cultures of rat hepatocytes. A 15-min vasopressin (10(-8) M) stimulation induced a reduction of glycogen content that reached a maximum 1-3 h later. Gap junction blockers, octanol or 18alpha-glycyrrhetinic acid, reduced the effect by 70%. The glycogenolytic response induced by Ca2+ ionophore 8-bromo-A-21387, which acts on each hepatocyte, was not affected by gap junction blockers. Moreover, the vasopressin-induced glycogenolysis was lower (70%) in dispersed than in reaggregated hepatocytes and in dispersed hepatocytes was not affected by gap junction blockers. In hepatocytes reaggregated in the presence of a synthetic peptide homologous to a domain of the extracellular loop 1 of the main hepatocyte gap junctional protein, vasopressin-induced glycogenolysis and incidence of dye coupling were drastically reduced. Moreover, gap junctional communication was detected between reaggregated cells, suggesting that hepatocytes with different vasopressin receptor densities become coupled to each other. The vasopressin-induced effect was not affected by suramin, ruling out ATP as a paracrine mediator. We propose that gap junctions allow for a coordinated vasopressin-induced glycogenolytic response despite the heterogeneity among hepatocytes.
Eugenín
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Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiogo, Chile.
González
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Sáez
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Sáez
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure*; D000442:Octanols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology*
D000442:Octanols; D014667:Vasopressins; D000255:Adenosine Triphosphate; D006003:Glycogen; D006034:Glycyrrhetinic Acid; D002118:Calcium