The activation of Na+-dependent efflux of Ca2+ from liver mitochondria by glucagon and β-adrenergic agonists

Abstract

The Na+-induced efflux of Ca2+ from liver mitochondria was activated by tissue pretreatment with 1 microM-adrenaline, 1 microM-isoprenaline, 10 nM-glucagon and 100 microM-cyclic AMP when 10 mM-lactate plus 1 mM-pyruvate were present in the perfusion medium. Infusion of the alpha 1-adrenergic agonist, phenylephrine (10 microM), was ineffective. The activation induced by the beta-adrenergic agonist, isoprenaline, was maximal after infusion of agonist for 2 min. The isoprenaline-induced activation was very marked (120-220%), with about 7 nmol of intramitochondrial Ca2+/mg of protein, but was not evident with greater than 15 nmol of Ca2+/mg. Ca2+ efflux in the absence of Na+ and in the presence of the Ca2+ ionophore A23187 was not affected by isoprenaline pretreatment over the range 6-23 nmol of internal Ca2+/mg. With 10 mM-lactate plus 1 mM-pyruvate in the perfusion medium, glucagon and isoprenaline infusion increased tissue cyclic AMP content about 8-fold and 3-fold respectively. With 10 mM-pyruvate alone, neither glucagon nor isoprenaline caused a significant increase in cyclic AMP. Omission of lactate also abolished the ability of glucagon, but not of isoprenaline, to activate the Na+-induced efflux of Ca2+. The data indicate that cyclic AMP may mediate the activation caused by glucagon, but provide no evidence that cyclic AMP is an obligatory link in the beta-adrenergic-induced activation.

Ca2+‐dependent inhibition by trifluoperazine of the Na+‐Ca2+ carrier in mitoplasts derived from heart mitochondria

“…The rate of Ca2+ release in the presence of ruthenium red alone (Na+-independent release; curves i and iv) was increased in mitoplasts (210+ 31%; mean&SE, 12 experiments), whereas the rate of Ca2+ efflux in the presence of Na+ was decreased (curves ii and v). Evidence based on relative sensitivities to lanthanides [16] and hormones [17] indicates that the Na+-independent process does not reflect a residual capacity of the Na+-Ca2+ carrier to operate in the absence of Na', but is attributable to a distinct system. This is substantiated by the relative sensitivities to trifluoperazine reported here.…”

Relation between mitochondrial calcium transport and control of energy metabolism

“…Stable changes in either Ca 2÷ transport pathway remain an attractive possible mechanism of hormone action, with an activation of the uniporter occurring in heart mitochondria as a consequence of a-adrenergic stimulation (Kessar and Crompton 1981 ), and an activation of the (inferred) antiporter of liver mitochondria occurring as a consequence of ~-adrenergic stimulation (Goldstone and Crompton 1982;Goldstone et al 1983). However, to date, such changes provide no explanation of the apparent release of mitochondrial Ca by a-agonists Reinhart et al 1982b Blackmore et al (1982), and Morgan et al (1983) that these agents interact with the mitochondria, presumably though a second messenger, alter the relative activities of uniport and antiport, and thus cause mitochondrial Ca 2÷ release is clearly consistent with some recent experimental evidence.…”

“…Thus, the effect of Na ÷ Goldstone et al 1983) and membrane potential (Zoccarato and Nicholls 1982) on Ca 2+ efflux is different in liver and heart. The relationship between these two parameters, i.e., K0.s for dehydrogenase activation and S0.s for Ca 2+ efflux, will determine whether there is any overlap between the mode of dehydrogenase control and that of [Ca2*]c buffering in any given tissue.…”

The role of ADP in the modulation of the calcium-efflux pathway in rat brain mitochondria

“…Pi load in the presence of variable amounts of the results of Goldstone et al (1983) showing that ADP. Total Ca2+-release rate was then determined the magnitude of the Ca2+ load limits the Ca2+-after the additions of Ruthenium Red, Na+ release rate measured after the simultaneous (10mM) and FCCP (1.2uM).…”