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Rapid Ca2+ influx induced by the action of dibutylhydroquinone and glucagon in the perfused rat liver.

ABSTRACT: Glucagon induces a slight Ca2+ efflux when administered to the perfused rat liver. However, the hormone promotes rapid and significant Ca2+ influx after the prior administration of 2, 5-di(t-butyl)-1,4-hydroquinone (BHQ), an agent that promotes Ca2+ release from the endoplasmic reticulum (ER). The concentrations of glucagon that promote Ca2+ influx are similar to those that promote glycogenolysis and gluconeogenesis in isolated hepatocytes. The permeable analogue of cAMP, but not that of cGMP, is able to duplicate the Ca2+-mobilizing effects of glucagon. The influx of Ca2+ into liver is blocked by Ni2+. Administration of sodium azide, an inhibitor of mitochondrial electron transport, also blocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed when azide administration is terminated. The actions of azide are evident within 60 s after administration or withdrawal, and also occur when either oligomycin or fructose is co-administered; this provides evidence for an effect of azide independent of cellular ATP depletion. Measurement of total calcium in mitochondria that were isolated rapidly from perfused livers after the combined administration of glucagon and BHQ confirmed that large quantities of extracellular Ca2+ had entered these organelles. These experiments provide evidence that in the perfused rat liver the artificial emptying of the ER Ca2+ pool allows glucagon to promote rapid and sustained Ca2+ influx that seems to terminate in mitochondria.

SUBMITTER: Applegate TL

PROVIDER: S-EPMC1218342 | biostudies-other | 1997 Apr

REPOSITORIES: biostudies-other

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The influx of Ca2+ induced by the administration of glucagon and Ca2+-mobilizing agents to the perfused rat liver could involve at least two separate pathways.

Project description:The Ca2+-mobilizing actions of ADP, ATP and epidermal growth factor (EGF) and their interaction with glucagon were studied in a perfused liver system incorporating a Ca2+-selective electrode. ADP (1-100 microM), ATP (1-100 microM) and EGF (10-50 nM) all induced a net efflux, followed by a net uptake of Ca2+ in the intact liver. The co-administration of glucagon (or of cyclic AMP) with these agents resulted in a synergistic potentiation of the Ca2+ uptake response in a way which resembles the synergism observed when glucagon is administered with phenylephrine, vasopressin or angiotensin [Altin & Bygrave (1986) Biochem J. 238, 653-661]. The inability of diltiazem, verapamil and nifedipine to inhibit the Ca2+-influx response suggests that the stimulation of Ca2+ influx does not occur through voltage-sensitive Ca2+ channels. By contrast, the synergistic effects of glucagon in the stimulation of Ca2+ influx are inhibited by 10 mM-neomycin, and a lowering of the extracellular pH to 6.8. Simultaneous measurements of perfusate Ca2+ and pH changes suggest that the Ca2+ influx response is not mediated by a Ca2+/H+ exchange. The inability of neomycin and low extracellular pH to inhibit the refilling of the hormone-sensitive pool of Ca2+, after the administration of Ca2+-mobilizing agents alone, provides evidence for the existence in liver of at least two Ca2+-influx pathways, or mechanisms for regulating Ca2+ influx.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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