Modulation of lipoprotein lipase in the intact rat by cholera toxin - An irreversible agonist of cyclic AMP

Abstract

Rats were injected intravenously with cholera toxin, a potent stimulator of adenylate cyclase, and lipoprotein lipase was determined in various organs and plasma. 16 h after cholera toxin injection, lipoprotein lipase activity increased 2–6-fold in heart, diaphragm and lung and decreased to one-third in adipose tissue. An increase in lipoprotein lipase activity was seen in the plasma and in the liver, as determined by antiserum to lipoprotein lipase. The increase in heart lipoprotein lipase was preceded by a rise in cyclic AMP and continued for 24 h when cyclic AMP returned to base-line levels. Both heparin-releasable and residual lipoprotein lipase increased in the heart, but to an unequal extent. The more pronounced rise in residual activity (up to 10-fold) could have contributed to an increase in the t 1 2 of heart lipoprotein lipase from 1.5 to 2.6 h. The relatively lower increase in heparin-releasable lipoprotein lipase could have been due to a loss of the enzyme from this compartment into the circulation. The effect of cholera toxin on heart and adipose tissue lipoprotien lipase was observed in fasted, fed and super-fed animals and thus appears to be independent of the nutritional state of the animal. Since cholera toxin not only mimics hormonal stimulation, but causes an exaggerated response to hormones, it made studies on some aspects of regulation of both the functional and storage forms of lipoprotein lipase in the intact organism possible.