The control of uncoupler-activated ATPase activity in rat liver mitochondria by adenine nucleotide transport. The effect of glucagon treatment.

Acute treatment of rats with glucagon increased the Vmax but did not change the Km (ATP) of uncoupler-activated ATPase in subsequently isolated hepatic mitochondria. The hormonal stimulation was evident in mitoplasts but not in submitochondrial particles nor after lysis of the mitochondria. The rate of Pi-ATP exchange of intact mitochondria was also increased by glucagon treatment. The hormonal stimulation of ATPase was dependent on concentration of the uncouplers, being absent at minimally effective concentrations while high concentrations inhibited the ATPase. Inhibitors of adenine nucleotide transport decreased ATPase activity without evidence of sigmoidicity in the response curves and produced linear Dixon plots indicating that the ATPase was limited by the rate of adenine nucleotide transport. Glucagon treatment did not change the number of binding sites for transport inhibitors. Glucagon stimulated the rate of transport of ATP as measured by accumulation of labeled nucleotide. This was found to be the consequence of an enlarged pool of exchangeable adenine nucleotides within mitochondria from glucagon-treated animals. This increase in mitochondrial nucleotides appears to explain a number of the effects of hormones on mitochondrial functions including the stimulation of uncoupler-activated ATPase activity.