Biochemical properties of cyclic nucleotide phosphodiesterase in metastasizing and nonmetastasizing rat mammary carcinomas.
The biochemical properties of cyclic nucleotide phosphodiesterases in a nonmetastasizing and a spontaneously metastasizing rat mammary carcinoma were compared. The phosphooiesterases in both tumors had a pH optimum of around 8.0 and preferentially hydrolysed cyclic purine nucleotides. The rate of hydrolysis of purine nucleotides in the nonmetastasizing tumor was two times higher than in the metastasizing tumor, but the rate of pyrimidine nucleotide hydrolysis was equal in both tumors. Theophylline, caffeine, and D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro20-1724) inhibited the enzyme activity in both tumors; the percent inhibition was the same by each inhibitor. The cyclic nucleotie phosphodiesterase activity in either tumor was stimulated by Mg++, Mn++, and Co++ and suppressed by Ca++, Zn,++, and Ni++. EDTA inhibited the activity below the basal level (activity in the absence of added cation), an this inhibition could be recovered up to the basal level by an equimolar quantity of either Mn++ or Mg++. Further stimulation of the enzyme activity with increasing concentrations of divalent cations was observed only with Mn++. Similar effects were observe with ethylene glycol bis(beta-aminoethyl ether)-tn,n-tetraacetic acid. The stimulatory cations affected both the low and high Michaelis constant (tkm) enzymes in these tumors by increasing the maximum velocity. In the low Km enzyme, the Km was also slightly increased. Neither guanosine 3',5'-cyclic monophosphate nor adenosine 3',5'-cyclic monophosphate had any effect on the hydrolysis of the other at physiologic levels.
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium; D003035:Cobalt; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D003864:Depression, Chemical; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008274:Magnesium; D008345:Manganese; D009362:Neoplasm Metastasis / Q000201:enzymology*; D009532:Nickel; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D015032:Zinc
D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003035:Cobalt; D002110:Caffeine; D008345:Manganese; D004533:Egtazic Acid; D009532:Nickel; D004492:Edetic Acid; D013806:Theophylline; D000242:Cyclic AMP; D006152:Cyclic GMP; D008274:Magnesium; D015032:Zinc; D002118:Calcium