Effect of 2'-deoxycoformycin infusion on S-adenosylhomocysteine hydrolase and the amount of S-adenosylhomocysteine and related compounds in tissues of mice.
Mice were given constant infusions of the adenosine deaminase inhibitor, 2'-deoxycoformycin, by i.p. implantation of microosmotic pumps, delivering the compound at a rate of 0.16 mg hr-1 kg-1. In accordance with published data, we observed that adenosine deaminase in most tissues was nearly completely inhibited. In addition, the S-adenosylhomocysteine hydrolase activity decreased slowly and showed a half-life in liver of about 4 hr. The rate and extent of the inactivation were highest in spleen. The amounts of adenosine, 2'-deoxyadenosine, S-adenosylhomocysteine, and S-adenosylmethionine were determined in treated animals and control animals. The tissue levels of adenosine and, to a lesser degree, S-adenosylhomocysteine and S-adenosylmethionine were critically dependent on the procedure used for processing the tissues. Lowest concentrations were observed when the organs were frozen in situ by liquid nitrogen. Treatment with 2'-deoxycoformycin induced no or a moderate increase in tissue content of adenosine and S-adenosylhomocysteine, whereas the amount of 2'-deoxyadenosine increased markedly, especially in spleen and thymus. 2'-Deoxycoformycin treatment caused an increase in adenosine and 2'-deoxyadenosine, but not S-adenosylhomocysteine, in serum of mice.
D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D043383:Adenosylhomocysteinase; D000818:Animals; D003070:Coformycin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives*; D006867:Hydrolases / Q000378:metabolism*; D007263:Infusions, Parenteral; D007583:Jejunum / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D009928:Organ Specificity; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D012263:Ribonucleosides; D006710:Homocysteine; D003070:Coformycin; D015649:Pentostatin; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D009700:Nucleoside Deaminases; D000241:Adenosine