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

A microtest has been devised for the rapid preliminary assay in vitro of the effect of over 100 drugs and inhibitors on African trypanosomes (Trypanosoma brucei and T. rhodesiense). Parasite motility and infectivity for mice are indexes, respectively, of respiration and glycolysis and of cell division; trypanocidal titers based on these indexes can show primary metabolic areas of drug attack. Various specific inhibitors have also been tested to detect metabolic sites which might be therapeutically vulnerable. RNA synthesis inhibitors are highly active (adenine nucleosides, daunorubicin, doxorubicin, chromomycin, actinomycin D, mitomycin C); the activity of the nucleoside cordycepin was increased in vitro and in vivo by an adenosine deaminase inhibitor. In view of the polyanionic nature of the trypanocide suramin, a series of polyanions was tested; several showed activity but only poly-d-glutamic acid was active in vivo. Among various miscellaneous inhibitors, quercetin, disulfiram, and the Ca-complexing agents arsenazo I and III showed marked activity, the latter exclusively on the arsenical-resistant T. brucei. The implications of these results for combination chemotherapy and depot prophylaxis (with polyanions) are indicated.
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PMID:Trypanocidal activity of antitumor antibiotics and other metabolic inhibitors. 66 98

A possible contribution of adenine nucleotides to the endogenous purinergic, A1-receptor-mediated inhibition of noradrenaline release was studied in rabbit occipito-parietal cortex slices. The slices were preincubated with [3H]-noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 6 pulses/100 Hz. A few experiments were carried out in rat occipito-parietal cortex slices. The A1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1-100 nmol/l) as well as the enzyme adenosine deaminase (0.1-10 U/ml) increased the electrically evoked overflow of tritiated compounds. The maximal increase was by about 85% for both DPCPX and adenosine deaminase. The increases obtained with maximally effective concentrations of DPCPX and adenosine deaminase were not additive. The alpha 1-adrenoceptor-selective agonist methoxamine (10 but not 1 mumol/l) reduced the evoked overflow. Its effect was antagonized by yohimbine 1 mumol/l but then not attenuated further by DPCPX 100 nmol/l. L-Glutamate (300 mumol/l-2.3 mmol/l) also reduced the evoked overflow of tritium. Its effect was not changed by yohimbine 1 mumol/l but greatly, and to the same extent, attenuated by DPCPX 100 nmol/l and adenosine deaminase 3 U/ml. Neither the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine nor omission of Mg++ changed the inhibition by glutamate. Glutamate did not alter the basal efflux of tritium from rabbit cortex slices under any experimental condition. In contrast, glutamate (100 mumol/l and 1 mmol/l) caused an immediate, marked and transient acceleration of tritium outflow from rat occipitoparietal cortex slices (medium without Mg++).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine but not an adenine nucleotide mediates tonic purinergic inhibition, as well as inhibition by glutamate, of noradrenaline release in rabbit brain cortex slices. 136 55

Bath application of glutamate at two concentration ranges, 10(-6)-10(-8) and 1-3 X 10(-3) M, effectively increased acetylcholinesterase activity in cerebellar slices obtained from 8-day-old rats. No such effect was seen in cerebellar slices of 7-week-old rats or cerebral slices of either 7-week or 8-day-old rats. Glutamic acid diethyl ester blocked the glutamate effect at both of these concentration ranges, suggesting that quisqualate-sensitive glutamate receptors are involved in regulation of acetylcholinesterase activity in early postnatal cerebellum. Since bath application of cyclic GMP at 10(-7)-10(-9) M increased the acetylcholinesterase activity in cerebellar slices of 8-day-old rats, it is possible that glutamate-dependent regulation of acetylcholinesterase activity is mediated by cyclic GMP. The observation that adenosine deaminase blocked the effect of glutamate completely at 10(-6)-10(-8) M and partially at 1-5 X 10(-3) M further suggests that release of adenosine is a link from enhanced cyclic GMP activity to activation of acetylcholinesterase.
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PMID:Glutamate-elicited stimulation of acetylcholinesterase activity in cerebellar slices from newborn rats. 287 25

The effects of L-glutamate and other dicarboxylic amino acids on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in slices of cerebral cortex from strain 2 guinea pigs were examined using tissue from animals at 39 days gestation to 7 days after birth. Responses to glutamate were inhibited completely by adenosine deaminase or theophylline unless histamine was present. When tested in the presence of adenosine, glutamate increased cyclic AMP accumulation up to 10-fold at 39 days gestation; the response was maximal at 52 days gestation, and both the efficacy and potency of glutamate declined thereafter. While the effects of glutamate were smaller in the presence of histamine plus theophylline, the developmental pattern was similar to that in the presence of adenosine. The relative potencies of D-aspartate, kainate, and alpha-methyl-DL-glutamate were much greater in fetal than in adult tissue. Glutamic acid diethyl ester, N-acetyl glutamate or 2,3-diaminopropionate had no effect in fetal tissue either in the presence or absence of glutamate. Responses to glutamate in adult tissue were much more dependent upon the presence of calcium ions than were those in fetal tissue. It was concluded that responses to glutamate involve mechanisms that differ in fetal and adult tissue.
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PMID:Ontogeny of adenosine 3',5'-monophosphate metabolism in guinea pig cerebral cortex. II. Development of responses to L-glutamate in the presence of adenosine or histamine. 288 13

The melanin-concentrating hormone and neuropeptide glutamic acid-isoleucine are expressed in neurons located mainly in the hypothalamus that project widely throughout the CNS. One of the melanin-concentrating hormone main targets is the medial mammillary nucleus, but the exact origin of these fibers is unknown. We observed melanin-concentrating hormone and neuropeptide glutamic acid-isoleucine immunoreactive fibers coursing throughout the mammillary complex, showing higher density in the pars lateralis of the medial mammillary nucleus, while the lateral mammillary nucleus showed sparse melanin-concentrating hormone innervation. The origins of these afferents were determined by using implant of the retrograde tracer True Blue in the medial mammillary nucleus. Double-labeled neurons were observed in the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus. A considerable population of retrogradely labeled melanin-concentrating hormone perikaryal profiles was also immunoreactive to neuropeptide glutamic acid-isoleucine (74+/-15% to 85+/-15%). The afferents from the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus to the medial mammillary nucleus were confirmed using implant of the anterograde tracer Phaseolus vulgaris leucoagglutinin. In addition, using double-labeled immunohistochemistry, we found no co-localization between neurons expressing melanin-concentrating hormone and adenosine deaminase (histaminergic marker) in the dorsal tuberomammillary nucleus. We hypothesize that these melanin-concentrating hormone projections participate in spatial memory process mediated by the medial mammillary nucleus. These pathways would enable the animal to look for food during the initial moments of appetite stimulation.
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PMID:Distribution of melanin-concentrating hormone neurons projecting to the medial mammillary nucleus. 1243 28