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)

Several adenosine analogs induce the functional and morphological differentiation of myelomonocytic leukemia cells. They can be classified into two types; i.e., those that do/do not require phosphorylation to induce the differentiation of leukemia cells. Neplanocin A, a potent S-adenosylhomocysteine hydrolase inhibitor, induces the differentiation of some leukemia cells without phosphorylation. On the other hand, deoxycoformycin (dCF), a potent adenosine deaminase inhibitor, also induces the myelomonocytic differentiation of leukemia cells when it is treated with deoxyadenosine (dAdo). This differentiation is inhibited by 5'-amino-deoxyadenosine, an inhibitor of (deoxy)adenosine kinase, suggesting that kinase-dependent phosphorylation is involved in the differentiation-inducing effect of dCF plus dAdo. Retinoids induce the differentiation of NB4 cells, a cell line derived from human promyelocytic leukemia. When used in combination with all-trans retinoic acid (ATRA), both NPA and dCF plus dAdo greatly enhance the granulocytic differentiation of NB4 cells. This enhancing effect is greatest when the cells are pretreated with NPA and then with ATRA. On the other hand, pre-exposure of NB4 cells to ATRA greatly potentiates the differentiation induced by dCF plus dAdo, while pretreatment with dCF plus dAdo before exposure to ATRA is less effective. The ATRA-induced differentiation of NB4 cells is effectively augmented by clinically applicable concentrations of these analogs. A clinical strategy that combines intermittent treatment with these analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.
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PMID:Adenosine analogs as possible differentiation-inducing agents against acute myeloid leukemia. 1043 63

Experimental evidence in animal models suggests that adenosine is involved in the regulation of digestive functions. This study examines the influence of adenosine on the contractile activity of human colon. Reverse transcription-polymerase chain reaction revealed A(1) and A(2a) receptor expression in colonic neuromuscular layers. Circular muscle preparations were connected to isotonic transducers to determine the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A(1) receptor antagonist), ZM 241385 (A(2a) receptor antagonist), CCPA (A(1) receptor agonist) and 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adenosine (CGS 21680; A(2a) receptor agonist) on motor responses evoked by electrical stimulation or carbachol. Electrically evoked contractions were enhanced by DPCPX and ZM 241385, and reduced by CCPA and CGS 21680. Similar effects were observed when colonic preparations were incubated with guanethidine (noradrenergic blocker), L-732,138, GR-159897 and SB-218795 (NK receptor antagonists). However, in the presence of guanethidine, NK receptor antagonists and N(omega)-propyl-L-arginine (NPA; neuronal nitric oxide synthase inhibitor), the effects of DPCPX and CCPA were still evident, while those of ZM 241385 and CGS 21680 no longer occurred. Carbachol-induced contractions were unaffected by A(2a) receptor ligands, but they were enhanced or reduced by DPCPX and CCPA, respectively. When colonic preparations were incubated with guanethidine, NK antagonists and atropine, electrically induced relaxations were partly reduced by ZM 241385 or NPA, but unaffected by DPCPX. Dipyridamole or application of exogenous adenosine reduced electrically and carbachol-evoked contractions, whereas adenosine deaminase enhanced such motor responses. In conclusion, adenosine exerts an inhibitory control on human colonic motility. A(1) receptors mediate direct modulating actions on smooth muscle, whereas A(2a) receptors operate through inhibitory nitrergic nerve pathways.
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PMID:A1 and A2a receptors mediate inhibitory effects of adenosine on the motor activity of human colon. 1901 12