RAPID CA2-RAT-LIVER( INFLUX INDUCED BY THE ACTION OF DIBUTYLHYDROQUINONE AND GLUCAGON IN THE PERFUSED)

Glucagon induces a slight Ca2+ efflux when administered to the perfuse d rat liver. However, the hormone promotes rapid and significant Ca2influx after the prior administration of 2,5-di(t-butyl)-1 ,4-hydroqui none (BHQ), an agent that promotes Ca2+ release from the endoplasmic r eticulum (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 s odium azide, an inhibitor of mitochondrial electron transport, also bl ocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed wh en azide administration is terminated. The actions of azide are eviden t within 60 s after administration or withdrawal, and also occur when either oligomycin or fructose is coadministered; this provides evidenc e for an effect of azide independent of cellular ATP depletion. Measur ement 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 the se 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.