Ca2+, K+ redistributions and alpha-adrenergic activation of glycogenolysis in perfused rat livers.
1. The alpha-adrenergic activation of glycogenolysis was investigated in isolated rat livers perfused in a non-recirculating system. Net uptake and/or release of Ca2+, K+ and H+ by the liver (measured by ion-selective electrodes) were correlated with the glycogenolytic effects of phenylephrine. Uptake and retention of 45Ca by the mitochondria of perfused livers were studied to obtain information on the role played by exchangeable mitochondrial calcium in alpha-adrenergic activation of glycogenolysis. 2. Between 1 and 5 min after starting the addition of phenylephrine a net release of Ca2+ was observed, this was paralleled by an uptake of K+. Production rates of glucose and lactate from endogenous glycogen started to increase at the same time. During the following minutes K+ was released. 2 mM EGTA and a high concentration of Mg2+ strongly diminished the ionic and metabolic responses to phenylephrine, 0.2 mM EGTA was less effective. 3. High concentrations of K+ prevented the metabolic response to phenylephrine but had no effect on the release of Ca2+ into the extracellular medium. Tetracaine activated glycogenolysis and suppressed all the effects of the alpha-adrenergic agonist. 4. Experiments with 45Ca provided no evidence for an alpha-adrenergic release of Ca2+ from the exchangeable mitochondrial pool. Incorporation of 45Ca into the mitochondria of perfused livers was enhanced by phenylephrine. 5. We propose that the alpha-adrenergic release of Ca2+ from a pool located close to the surface of the cell is capable of triggering the glycogenolytic response.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats
D000316:Adrenergic alpha-Agonists; D008112:Liver Glycogen; D010656:Phenylephrine; D011188:Potassium; D002118:Calcium