title: Effects of nucleotides and nucleosides on the activity of cyclic AMP phosphodiesterase from rat brain.
abstract: Cyclic nucleotides phosphodiesterase (PDE) was prepared from cerebrum of male rats and its kinetic properties were studied. The phosphodiesterase preparation exhibited two Michaelis constants, 8.7 microM and 83.3 microM. Adenine derivatives such as adenosine, 5'-AMP and 2'(3')-AMP inhibited the PDE activity at concentrations exceeding 7 X 10(-3)M, and 2'-deoxyadenosine inhibited the activity at lower concentrations (Ki = 1.8 X 10(-3)M); its inhibiting efficacy was almost the same as that of theophylline (Ki = 1.9 X 10(-3)M). Guanine derivatives, on the other hand, showed several different effects. Guanosine and 3',5'-cyclic GMP activated the PDE at 10(-5) M and inhibited at concentrations higher than 10(-4)M. 2'(3')-GMP showed no effect, but 5'-GMP activated markedly at concentrations of 10(-3) to 10(-2)M. Thymidine showed slight inhibitory effect, but cytidine or 2'-deoxycytidine had no effect. Uracil derivatives such as uridine, 5'-UMP, 3',5'-cyclic UMP and 2'(3')-UMP activated the PDE at concentrations exceeding 3 X 10(-3) M. These results indicate that individual nucleosides and nucleotides exhibit structure-activity relationship with PDE.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D006152:Cyclic GMP / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009705:Nucleosides / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003839:Deoxyadenosines; D009705:Nucleosides; D009711:Nucleotides; D006157:Guanosine Monophosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP