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

The effects of benzodiazepines, GABA and adenosine on distress-induced hyperemotionality and gastric lesion formation were investigated in rats. Hyperemotionality such as struggling, vocalization and defecation evoked immediately after immobilization stress were attenuated by diazepam, adenosine or adenosine plus diazepam. Conversely, pretreatment with these drugs produced rapid and potent exacerbation of gastric lesions observed after 12 h of stress. The potent adenosine A1-receptor agonist N6-cyclohexyl adenosine (CHA) markedly inhibited the distress-evoked hyperemotional behaviors and potentiated the ulceration. gamma-Aminobutyric acid (GABA), muscimol, a GABA receptor agonist, and aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, attenuated both stress-induced hyperemotionality and ulceration. The inhibitory effects of diazepam and GABA on hyperemotionality were reversed, respectively, by Ro15-1788, a benzodiazepine receptor antagonist, and bicuculline, a GABA receptor antagonist. The stimulatory effect of CHA on stress ulceration was potentiated by bicuculline but was not affected by Ro15-1788 or by picrotoxin, a chloride channel inhibitor. These results suggest that the mechanism involved in gastric lesion formation induced by immobilization stress may be different from that in hyperemotional behavior, and that the activation of GABAergic neurons may act as a central modulating factor in the hyperemotionality and ulceration induced by immobilization stress.
 ...
PMID:The role of adenosinergic, GABAergic and benzodiazepine systems in hyperemotionality and ulcer formation in stressed rats. 287 82

This study examined the ability of an adenosine kinase inhibitor (5'-amino-5'-deoxyadenosine; NH2dAD), an adenosine deaminase inhibitor (2'-deoxycoformycin), and combinations of these agents to produce a peripheral modulation of the pain signal in the low concentration formalin model. Drugs were administered in combination with 0.5% formalin, or into the contralateral hindpaw to test for systemic effects, and episodes of flinching behaviors determined. Coadministration of NH2dAD 0.1-100 nmol with formalin produced antinociception as revealed by an inhibition of flinching behaviors. This action was peripherally mediated as it was not seen following contralateral administration of the NH2dAD, and was due to accumulation of adenosine and activation of cell surface adenosine receptors as it was blocked by the adenosine receptor antagonist caffeine. Antinociception was intensity-dependent, as it was not seen when higher concentrations of formalin (0.75%, 1.5%) were used. The coadministration of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine revealed the presence of an inhibitory tone of adenosine when the intrinsic antinociceptive effect of NH2dAD was obscured by the solvent or the stimulus intensity. 2'-Deoxycoformycin 0.1-100 nmol did not produce any intrinsic effect, but 100 nmol coadministered with low concentrations of NH2dAD, which lacked an intrinsic effect, augmented antinociception by NH2dAD. Again, this was a peripheral rather than a systemic response. The combined action of the adenosine kinase and deaminase inhibitors was completely reversed by coadministration of caffeine. Antinociception with NH2dAD is observed at higher concentrations of formalin in second trial experiments. This study demonstrates a peripheral antinociceptive action mediated by endogenous adenosine which accumulates following the peripheral inhibition of adenosine kinase; this action is due to activation of an adenosine A1 receptor.
 ...
PMID:Peripheral antinociceptive effect of an adenosine kinase inhibitor, with augmentation by an adenosine deaminase inhibitor, in the rat formalin test. 951 63

Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO2, pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A1 adenosine receptor antagonist. Isohydric hypercapnia (20% CO2, pH 7.3), but not isocapnic acidosis (5% CO2, pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5'-nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A1 receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia.
 ...
PMID:Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats. 1677 47