The metabolism of cyclic nucleotides in the guinea-pig pancreas. Cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase.
Both cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase were recovered mainly from the supernatant fractions of guinea-pig pancreas, but a higher proportion of the activity of the former was associated with the pellet fractions. The activities in the supernatant were not separated by gel filtration, but were clearly separated by subsequent chromatography on an anion-exchange resin. The activities of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase had high-affinity (K(m) 6.5+/-1.1mum and 31.9+/-3.9mum respectively) and low-affinity (K(m) 0.56+/-0.05mm and 0.32+/-0.03mm respectively) components. The activity of neither enzyme was affected by the pancreatic secretogens, cholecystokinin-pancreozymin, secretin and carbachol. Removal of ions by gel filtration resulted in a marked reduction in cyclic nucleotide phosphodiesterase activity, which could be restored by addition of Mg(2+). Mn(2+) (3mm) was as effective as Mg(2+) (3mm) in the case of cyclic AMP phosphodiesterase, but was less than half as effective in the case of cyclic GMP phosphodiesterase. The metal-ion chelators, EDTA and EGTA, also decreased activity. Ca(2+) (1mm) did not affect the activity of cyclic nucleotide phosphodiesterase when the concentration of Mg(2+) was 3mm. At concentrations of Mg(2+) between 0.1 and 1mm, 1mm-Ca(2+) was activatory, and at concentrations of Mg(2+) below 0.1mm, 1mm-Ca(2+) was inhibitory. These results are discussed in terms of the possible significance of cyclic nucleotide phosphodiesterase in the physiological control of cyclic nucleotide concentrations during stimulus-secretion coupling.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004356:Drug Storage; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D010208:Papaverine / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology; D014970:Xanthines / Q000494:pharmacology
D002413:Cations, Divalent; D014970:Xanthines; D010208:Papaverine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP