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

Publisher Website
Google Scholar
Abstract
The Na+-induced efflux of Ca2+ from [rat] liver mitochondria was activated by tissue pretreatment with 1 .mu.M-adrenaline [epinephrine], 1 .mu.M-isoprenaline, 10 nM-glucagon and 100 .mu.M-cAMP when 10 mM-lactate plus 1 mM-pyruvate were present in the perfusion medium. Infusion of the .alpha.1-adrenergic agonist, phenylephrine (10 .mu.M), 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 .apprx. 7 nmol of intramitochondrial Ca2+/mg of protein, but was not evident with > 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 cAMP content .apprx. 8-fold and 3-fold, respectively. With 10 mM-pyruvate alone, neither glucagon nor isoprenaline caused a significant increase in cAMP. Omission of lactate also abolished the ability of glucagon, but not of isoprenaline, to activate the Na+-induced efflux of Ca2+. Cyclic AMP may mediate the activation caused by glucagon, but provide no evidence that cAMP is an obligatory link in the .beta.-adrenergic-induced activation.