Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We employed an isolated guinea-pig heart model perfused at constant pressure (70 cmH2O) to test the hypothesis that inhibition of adenosine metabolism increases interstitial adenosine concentrations (as measured with epicardial discs) and coronary flow. Iodotubercidin (ITU, 1 microM) and EHNA (erythro-9-[2-hydroxy-3-nonyl] adenine, 5 microM) were used to inhibit adenosine kinase and deaminase, respectively during control conditions and during metabolic stimulation with 1 microM isoproterenol. The adenosine receptor blocker 8-phenyltheophylline (8-PT) was used during control conditions to assess whether the response seen was adenosine specific. ITU plus EHNA decreased heart rate (202 +/- 10 to 136 +/- 11 beats/min) and increased coronary flow (8.2 +/- 0.3 to 12.4 +/- 0.9 ml/min/g) without a change in MVO2, developed pressure or dP/dt. ITU plus EHNA increased adenosine concentrations in epicardial fluid (0.24 +/- 0.07 microM to 1.02 +/- 0.09 microM) and venous effluent (40 +/- 3 nM to 262 +/- 32 nM) during control conditions, and adenosine release increased from 389 +/- 96 pmols/min/g to 3480 +/- 365 pmols/min/g. 8-PT infusion reversed the effects on heart rate and coronary flow and resulted in a persistent elevation of epicardial fluid adenosine concentrations. During metabolic stimulation with 1 microM isoproterenol, ITU plus EHNA significantly limited the increase in heart rate and ventricular developed pressure and dP/dt while coronary flow increased to a significantly greater extent. Myocardial oxygen consumption was similar during metabolic stimulation between the two groups (vehicle vs. ITU plus EHNA). Epicardial fluid adenosine concentration in the vehicle-treated group increased from 0.17 +/- 0.3 microM to 0.34 +/- 0.02 microM at 15 min of isoproterenol stimulation whereas it increased from 1.10 +/- 0.02 microM to 2.90 +/- 0.46 microM in the ITU plus EHNA-treated group. Inhibition of adenosine metabolism during metabolic stimulation significantly increased venous adenosine concentrations and adenosine release and reduced inosine and hypoxanthine release proportionately. The release of adenosine+inosine+hypoxanthine was unchanged. Inhibition of adenosine metabolism provides evidence supporting the hypothesis that adenosine plays a role in regulating coronary vascular resistance as well as influencing heart rate and ventricular inotropy.
J Mol Cell Cardiol 1992 Nov
PMID:Inhibition of adenosine metabolism increases myocardial interstitial adenosine concentrations and coronary flow. 147 23

The contribution of 5'-nucleotidase and AMP-deaminase to adenine nucleotide degradation in human cardiomyocytes isolated from diseased or normal heart was investigated. The preparation used contained 30 to 50% of viable cells and the nucleotide degradation was stimulated by addition of deoxyglucose and oligomycin. To distinguish pathways of nucleotide degradation, adenosine deaminase was inhibited by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Under these conditions, ATP concentration was decreased by 60% after 45 min of incubation. Simultaneously, increases in intra- and extracellular catabolite concentrations have been observed. Adenosine was the predominant catabolite found in both the cells and in the extracellular medium accounting for more than 70% of all degradation products. Intracellular adenosine concentration rose to 300 times greater than that outside the cell. An increase in intra- and extracellular inosine was also seen. Only a small increase of IMP concentration was observed. No hypoxanthine accumulation was found. No significant change in initial adenine nucleotide concentrations were observed in isolated cells during aerobic incubation without deoxyglucose and oligomycin. In conclusion, a pathway involving adenosine production appears to be the principal route of nucleotide degradation in human cardiomyocytes.
J Mol Cell Cardiol 1992 Jan
PMID:Adenine nucleotide catabolism and adenosine formation in isolated human cardiomyocytes. 156 34

The present report demonstrates the presence of antianandamide and anticannabinoid receptor 1 immunopositive material on the saphenous vascular endothelium. The endogenous cannabinoid, anandamide, in a dose-dependent manner stimulated the release of nitric oxide (NO) from saphenous vein, internal thoracic artery and right atrium tissue segments in vitro. This process can be antagonized by the nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M; 3.4+/-0.9 nM NO; P<0.01 compared to anandamide alone), as well as by the cannabinoid receptor I antagonist SR 141716A (2.9+/-1.0 nM NO; P<0.01). Furthermore, in the presence of varying concentrations of methylarachidonylfluorophosphonate, an anandamide amidase inhibitor, 10(-8) M anandamide stimulates a higher peak level of NO that remains elevated for a longer period of time (P<0.05) compared to anandamide alone, demonstrating the presence of anandamide amidase in human vascular tissues. Morphine, as anandamide, can stimulate the release of NO from right atria. This process can be inhibited by the opiate receptor antagonist naloxone and the NOS inhibitor L-NAME. As expected SR 141716A (10(-6) M; 26+3.8 NO nM in the presence of 10(-7) M morphine) did not antagonize morphine's ability to release NO. Taken together, the data demonstrate that cannabinoid signalling is involved with the regulation of the microvascular environment.
Int J Cardiol 1998 Apr 30
PMID:Pharmacological evidence for anandamide amidase in human cardiac and vascular tissues. 968 88

This review focuses on recent advances in the association between left ventricular hypertrabeculation/noncompaction (LVHT), a form of unclassified cardiomyopathy, and neuromuscular disorders (NMD). So far, LVHT has been found in single patients with dystrophinopathy, dystrobrevinopathy, laminopathy, zaspopathy, myotonic dystrophy, infantile glycogenosis type II (Pompe's disease), myoadenylate-deaminase deficiency, mitochondriopathy, Barth syndrome, Friedreich ataxia, and Charcot-Marie-Tooth disease. Most frequently LVHT is found in patients with Barth syndrome and mitochondrial disorders. The prevalence of LVHT in NMD patients is not known. On the contrary, NMD can be detected in up to four fifths of the patients with LVHT. Because LVHT is associated with an increased risk of rhythm abnormalities and heart failure, it is essential to detect LVHT as soon as possible. Because of adequate therapeutic options, all patients with NMD should undergo a comprehensive cardiological examination as soon as their neurological diagnosis is established. In reverse, all patients with LVHT should undergo a comprehensive neurological investigation following the detection of LVHT.
Int J Cardiol 2006 Jun 28
PMID:Neuromuscular implications in left ventricular hypertrabeculation/noncompaction. 1636 74