Rapid Ca2+ influx induced by the action of dibutylhydroquinone and glucagon in the perfused rat liver.
Glucagon induces a slight Ca2+ efflux when administered to the perfused rat liver. However, the hormone promotes rapid and significant Ca2+ influx after the prior administration of 2, 5-di(t-butyl)-1,4-hydroquinone (BHQ), an agent that promotes Ca2+ release from the endoplasmic reticulum (ER). The concentrations of glucagon that promote Ca2+ influx are similar to those that promote glycogenolysis and gluconeogenesis in isolated hepatocytes. The permeable analogue of cAMP, but not that of cGMP, is able to duplicate the Ca2+-mobilizing effects of glucagon. The influx of Ca2+ into liver is blocked by Ni2+. Administration of sodium azide, an inhibitor of mitochondrial electron transport, also blocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed when azide administration is terminated. The actions of azide are evident within 60 s after administration or withdrawal, and also occur when either oligomycin or fructose is co-administered; this provides evidence for an effect of azide independent of cellular ATP depletion. Measurement of total calcium in mitochondria that were isolated rapidly from perfused livers after the combined administration of glucagon and BHQ confirmed that large quantities of extracellular Ca2+ had entered these organelles. These experiments provide evidence that in the perfused rat liver the artificial emptying of the ER Ca2+ pool allows glucagon to promote rapid and sustained Ca2+ influx that seems to terminate in mitochondria.
Applegate
T L
TL
Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, ACT 0200, Australia.
Karjalainen
A
A
Bygrave
F L
FL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D019810:Sodium Azide
D000975:Antioxidants; D001386:Azides; D004791:Enzyme Inhibitors; D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; D005934:Glucagon; D019810:Sodium Azide; D000242:Cyclic AMP; D000252:Calcium-Transporting ATPases; D002118:Calcium