Author:
Koukoui O.,Boucherie S.,Sezan A.,Prigent S.,Combettes L.
Abstract
Coordination of intercellular Ca2+signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2αand PGE2, may modify these hepatocyte functions by inducing Ca2+increase, but very little is known about the organization of the Ca2+signals induced by these agonists. We studied Ca2+signals induced by PGF2αand PGE2in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+oscillations, neither PGF2αnor PGE2induced coordinated Ca2+oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol ( 1 , 4 , 5 )trisphosphate [Ins( 1 , 4 , 5 )P3] assays and the increase in Ins( 1 , 4 , 5 )P3receptor sensitivity to Ins( 1 , 4 , 5 )P3observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins( 1 , 4 , 5 )P3formed by these prostaglandins. Furthermore, when PGE2and PGF2αwere added just before norepinephrine, they favored the coordination of Ca2+signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (≥2 h) treatment with PGF2α, thereby preventing the coordination of Ca2+oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2α, may enhance or diminish the propagation of Ca2+signals. They may therefore contribute to the fine tuning of Ca2+wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.
Publisher
American Physiological Society
Subject
Physiology (medical),Gastroenterology,Hepatology,Physiology