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Comparative Adenylate Cyclase Activities in Homogenate and Plasma Membrane Fractions of Morris Hepatoma 5123tc (h)¹

Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 0W0

Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activities of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E₁, and insulin.

The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'-triphosphate concentration of 3.2 mM; if the substrate affinity (K_m adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide.

Glucagon (5.6 µM) significantly stimulated adenylate cyclase in both fractions of hepatoma and liver; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity) for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively.

Sodium fluoride (10 mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 µM) enhanced the liver and hepatoma homogenate activities 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activities were not increased. Prostaglandin E₁ (56.6 µM) significantly increased adenylate cyclase activities of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 µM) did not significantly alter adenylate cyclase activities in any of the preparations.

¹ This project was supported by the Medical Research Council of Canada, Grant MA-4476.

Received 6/18/74. Accepted 11/13/74.