On the mechanism by which hormones induce the release of Ca2+ from mitochondria in the liver cell

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Abstract
The abilities of dinitrophenol, NaCl, Ruthenium Red and the Ca2+-selective ionophore A23187 [calcimycin]to release 45Ca2+ from isolated rat hepatocytes and liver mitochondria (incubated at 37.degree. C in the presence of 0.1 .mu.M free Ca2+, Mg2+, ATP and phosphate ions) were compared with the action of adrenaline [epinephrine, E] on 45Ca2+ release from isolated hepatocytes. The effects of E were most closely described by those of the ionophore A23187. In isolated hepatocytes, a release of 45Ca2+ and stimulation of O2 utilization similar to that induced by E was observed in the presence of 500 and 20 .mu.M arachidonic acid, respectively. The effect of arachidonic acid on 45Ca2+ release was not specific for this unsaturated fatty acid. Inhibitors of arachidonic acid metabolism, including indomethacin and eicosa-5,8,11,14-tetraenoic acid, did not block the effects of E on 45Ca2+ or glucose release from isolated hepatocytes. The ability of E to stimulate 45Ca2+ release from isolated hepatocytes was rapidly reversed after the subsequent addition of phenoxybenzamine to the cell suspension, and was completely blocked by 0.5 mM dibucaine. The results are consistent with the action of a Ca2+-selective ionophore in the mechanism by which E induces the release of Ca2+ from mitochondria in the liver cell and indicate that it is unlikely that arachidonic acid or a metabolite of arachidonic acid is involved in this process.