Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2'-Deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase (ADA), is increasingly used as a tool to investigate adenosine metabolism and neuromodulation. To advance further the usefulness of DCF for studies of purines in the CNS, we determined the inhibitory potency of this compound against ADA and adenylate deaminase (AMPDA) in brain, the rate of ADA recovery in various brain regions after single or repeated intraperitoneal DCF administrations, and the effect of DCF on several neurotransmitter synthetic enzymes. In vitro, the Ki values for inhibition of ADA and AMPDA were found to be 23 pM and 233 microM, respectively. In vivo, DCF inhibited ADA with ED50 values ranging from 155 to 280 micrograms/kg at 2 h posttreatment, and 98% inhibition was achieved with 1 mg/kg. AMPDA activity was not affected by doses up to 5.0 mg/kg. In contrast to the greater than 95% inhibition of ADA seen 1 day after DCF at 5 mg/kg, the effectiveness of a second similar DCF treatment on the activity that had recovered by 14 days was dramatically reduced. Eight days after DCF treatment with doses of 5-50 mg/kg, the degree of ADA activity recovery in 10 brain regions examined was similar; it averaged 35% of control values at the low dose but showed some heterogeneity, ranging from 15 to 54% of control values, at the higher doses. Forty days after treatment with a single dose of 5 mg/kg, ADA activity recovered by 68-78% of control values in brain regions with normally high levels of activity and by 44-59% of control values in other regions. The activities of choline acetyltransferase, glutamic acid decarboxylase, and histidine decarboxylase (an enzyme colocalized with ADA in hypothalamic neurons) were unaffected by DCF treatment, a result suggesting the lack of a generalized neurotoxic effect. The very low doses of DCF required for ADA inhibition in vivo are consistent with the high potency of this drug against ADA in vitro, and any physiological effects observed at low doses might therefore be ascribed to inhibition of ADA.
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PMID:2'-Deoxycoformycin inhibition of adenosine deaminase in rat brain: in vivo and in vitro analysis of specificity, potency, and enzyme recovery. 217 70

Neurons immunoreactive for the enzyme adenosine deaminase (ADA) in the posterior basal hypothalamus of the rat have a distribution pattern similar to those immunoreactive for histidine decarboxylase (HDC) and are particularly numerous in the tuberal (TM), caudal (CM) and postmammillary caudal (PCM) hypothalamic magnocellular nuclei which harbor neurons containing glutamic acid decarboxylase (GAD). The extent to which these enzymes coexist within neurons of these hypothalamic regions was examined using either serial sections or simultaneous immunostaining for ADA and HDC or GAD in the same section. Analysis of serial sections revealed neuronal coexistence of ADA with HDC or GAD in both TM and CM. In addition some neurons in CM, the only area examined for triple coexistence, were found to contain all three enzymes. In sections processed for ADA simultaneously with HDC or GAD, nearly all ADA-immunoreactive neurons in TM, CM, and PCM as well as those scattered between these nuclei were found to contain HDC, and nearly all contained GAD. Exceptions to this, however, were small cells located lateral to the posterior arcuate nucleus, which appeared to contain ADA but not HDC, and large neurons located at the anterior extreme of TM, which appeared to contain ADA but not GAD. The relatively few ADA- compared with GAD-containing neural systems in brain, together with the presence of ADA in GAD-containing hypothalamic magnocellular neurons, which appear to have widespread projections throughout the brain, indicate that ADA may be a convenient immunohistochemical marker for anatomical investigations of these projections.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coexistence of adenosine deaminase, histidine decarboxylase, and glutamate decarboxylase in hypothalamic neurons of the rat. 407 33

Using extracellular single-unit recordings, we have determined the characteristics of neurons in the ventral tuberomammillary nucleus (VTM) of wild-type (WT) and histidine decarboxylase knock-out (HDC-KO) mice during the sleep-waking cycle. The VTM neurons of HDC-KO mice showed no histamine immunoreactivity, but were immunoreactive for the histaminergic (HA) neuron markers adenosine deaminase and glutamic acid decarboxylase 67. In the VTM of WT mice, we found waking (W)-specific, non-W-specific W-active, sleep-active, W and paradoxical sleep (PS)-active, and state-indifferent neuron groups. We previously demonstrated in WT mice that only W-specific neurons are histaminergic and that they are characterized by a triphasic broad action potential. In the VTM of HDC-KO mice, we found all these groups of state-dependent and state-indifferent neurons, including W-specific neurons that were characterized by a triphasic broad action potential and a W-specific slow tonic discharge, as in WT mice. The W-specific neurons ceased firing before the onset of electroencephalogram (EEG) synchronization, the first EEG sign of sleep, and remained silent during both slow-wave sleep (SWS) and PS. At the transition from SWS to W, they discharged after the onset of EEG activation, the first EEG sign of W. They either responded to an arousing stimulus with a long delay or did not respond. They therefore presented exactly the same characteristics as those seen in the VTM of WT mice. Thus VTM neurons deprived of their natural transmitter histamine still exhibit the firing properties of W-specific HA neurons.
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PMID:Sleep-waking discharge of ventral tuberomammillary neurons in wild-type and histidine decarboxylase knock-out mice. 2106 Jul 18