The activation of Na+-dependent efflux of Ca2+ from liver mitochondria by glucagon and beta-adrenergic agonists.
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.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D005934:Glucagon; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium