Title : Rat brain adenosine deaminase after 2'-deoxycoformycin administration: biochemical properties and evidence for reduced enzyme levels detected by 2'-[3H]deoxycoformycin ligand binding.

Pub. Date : 1992 Feb

PMID : 1729390






21 Functional Relationships(s)
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1 Rat brain adenosine deaminase after 2"-deoxycoformycin administration: biochemical properties and evidence for reduced enzyme levels detected by 2"-[3H]deoxycoformycin ligand binding. Pentostatin adenosine deaminase Rattus norvegicus
2 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
3 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
4 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
5 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
6 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
7 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
8 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
9 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
10 Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2"-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Pentostatin adenosine deaminase Rattus norvegicus
11 Here, we investigated the biochemical properties of ADA and the basis for its reduced activity after DCF treatment. Pentostatin adenosine deaminase Rattus norvegicus
12 It was found that much higher doses of DCF were required to inhibit ADA in DCF-treated compared with drug-naive animals. Pentostatin adenosine deaminase Rattus norvegicus
13 It was found that much higher doses of DCF were required to inhibit ADA in DCF-treated compared with drug-naive animals. Pentostatin adenosine deaminase Rattus norvegicus
14 Fourteen days after DCF administration, reduced ADA activity in brain homogenates was due to a decrease in Vmax, rather than to an altered Km of ADA for adenosine. Pentostatin adenosine deaminase Rattus norvegicus
15 The IC50 value for DCF inhibition of ADA in hypothalamus was unchanged. Pentostatin adenosine deaminase Rattus norvegicus
16 However, the Ki for DCF inhibition of ADA in whole brain increased by fivefold. Pentostatin adenosine deaminase Rattus norvegicus
17 Sucrose gradient analysis of brain ADA revealed only one corresponding peak of activity and [3H]DCF-labeled ADA in DCF-treated and control rats. Pentostatin adenosine deaminase Rattus norvegicus
18 Sucrose gradient analysis of brain ADA revealed only one corresponding peak of activity and [3H]DCF-labeled ADA in DCF-treated and control rats. Pentostatin adenosine deaminase Rattus norvegicus
19 Sucrose gradient analysis of brain ADA revealed only one corresponding peak of activity and [3H]DCF-labeled ADA in DCF-treated and control rats. Pentostatin adenosine deaminase Rattus norvegicus
20 Sucrose gradient analysis of brain ADA revealed only one corresponding peak of activity and [3H]DCF-labeled ADA in DCF-treated and control rats. Pentostatin adenosine deaminase Rattus norvegicus
21 A radioligand filtration assay with [3H]DCF was developed to assess the effects of DCF on ADA protein levels. Pentostatin adenosine deaminase Rattus norvegicus