Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes

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Isolated rat hepatocytes do not actively accumulate Ca2+ during prolonged incubation in vitro; however, these cells do exhibit a limited exchange of intracellular with extracellular Ca2+. The exchangeable pool represents about 2 nmol of Ca2+ per mg of protein. In medium containing either a low (20 μM) or high (1 mM) concentration of Ca2+, the divalent cation ionophore, A23187 (at concentrations of 0.03-0.1 nmol/mg of protein), causes release of 45Ca2+ from this exchangeable pool but does not allow net influx of extracellular Ca2+ detectable by the use of a Ca2+-sensitive electrode. Like A23187, the hormones norepinephrine, vasopressin, and glucagon (at concentrations that stimulate gluconeogenesis) each induces a similar net efflux of Ca2+. Treatment with one hormone decreases the subsequent reponse to the others, whereas treatment with A23187 abolishes the hormonal effects upon both Ca2+ release and gluconeogenesis. The action of norepinephrine, but not of glucagon, upon Ca2+ efflux is prevented by the α-adrenergic antagonist, phenoxybenzamine. The action of norepinephrine is not prevented by the β-adrenergic antagonist, propranolol. Together these results indicate that the release of Ca2+ from a common pool of exchangeable Ca2+ is important to the action of a variety of hormones on hepatocytes. This Ca2+ pool in the isolated hepatocyte is characterized as being similar in size and having exchange kinetics that are comparable to those reported for the major intracellular pool of Ca2+ in the intact liver. The possibility that this pool is intramitochondrial calcium is discussed.

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