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)

Endogenous purinergic systems mediating antinociception, and their interactions with opioids, were characterized following intrathecal (i.t.) administration of inhibitors of adenosine clearance in mice. 5'-Amino,5'-deoxyadenosine (5'-NH2dAdo), an inhibitor of adenosine kinase, induced significant antinociception after i.t. injection and enhanced antinociception induced by selected opioids (i.t.). Isobolographic analysis of antinociception following coadministration (i.t.) of 5'-NH2dAdo with opioids revealed additive interactions with mu-, and synergistic interactions with delta-, opioid receptor-selective agonists. Inhibitors of adenosine deaminase, deoxycoformycin and erythro-9-(2-hydroxy-3nonyl) adenine (EHNA), generally failed to induce antinociception when administered (i.t.) alone or to enhance opioid (i.t.)-induced antinociception, however, was significantly enhanced by either 5'-NH2dAdo or deoxycoformycin. These results confirm different physiologic roles for adenosine kinase and adenosine deaminase in spinal purinergic systems. 5'-NH2dAdo interactions with opioid receptor-selective agonists demonstrate significant, but heterogeneous interactions between endogenous adenosine and opioid spinal systems mediating antinociception.
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PMID:Adenosine kinase and adenosine deaminase inhibition modulate spinal adenosine- and opioid agonist-induced antinociception in mice. 769 11

1. An eye-cup preparation in anaesthetized rabbits was used to examine opioid modulation of acetylcholine (ACh) release from cholinergic neurones in the retina. 2. The mu-opioid receptor agonist, [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAMGO), when applied locally to the retina at concentrations between 1-30 microM significantly increased the light-evoked release of ACh. The effect of DAMGO was completely blocked by the selective mu-receptor antagonist CTOP but the kappa-receptor antagonist nor-binaltorphimine (norBNI) did not affect the action of DAMGO on ACh release indicating that the opioid produced its effect by activation of mu-receptors (the rabbit retina has negligible delta-receptors). 3. Blockade with bicuculline and strychnine of GABAergic and glycinergic inputs to the cholinergic neurones did not affect the action of DAMGO on ACh release. Also DAMGO did not reduce the potassium-evoked release of either GABA or glycine from rat isolated retinas. 4. Exposure of the rabbit retina to a combination of an A1-adenosine receptor antagonist, 8-cyclopentyl-1,3 dipropylxanthine (DPCPX), and adenosine deaminase did not affect the enhancing action of DAMGO on the light-evoked release of ACh. 5. When the retina in the rabbit eye-cup was exposed to kainate, the release of ACh was increased by approximately three times the resting release. In the presence of DAMGO the kainate-evoked release of ACh was enhanced by 44%. 6. These experiments show that activation of mu-opioid receptors by DAMGO increases the release of ACh elicited by physiological stimulation (flickering light). Since we could find no evidence thatDAMGO reduces inhibitory inputs to the cholinergic neurones, it seems that the enhancing action ofDAMGO on the light-evoked release of ACh involves a direct excitatory effect rather than disinhibition.This conclusion is supported by the enhancing action of DAMGO on the kainate-evoked release of ACh because kainate is thought to act directly on the cholinergic neurones.
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PMID:Enhancement of retinal acetylcholine release by DAMGO: possibly a direct opioid receptor-mediated excitatory effect. 785 68

This study investigated the involvement of the adenosinergic system in antiallodynia induced by exercise in an animal model of complex regional pain syndrome type I (CRPS-I). Furthermore, we analyzed the role of the opioid receptors on exercise-induced analgesia. Ischemia/reperfusion (IR) mice, nonexercised and exercised, received intraperitoneal injections of caffeine (10mg/kg, a non selective adenosine receptor antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (0.1mg/kg, a selective adenosine A receptor antagonist), ZM241385 (3mg/kg, a selective adenosine A receptor antagonist), adenosine deaminase inhibitor erythro-9-(2-hydroxy-3nonyl) adenine [(EHNA), 5mg/kg, an adenosine deaminase inhibitor] or naloxone (1mg/kg, a nonselective opioid receptor antagonist). The results showed that high-intensity swimming exercise reduced mechanical allodynia in an animal model of CRPS-I in mice. The antiallodynic effect caused by exercise was reversed by pretreatment with caffeine, naloxone, DPCPX but it was not modified by ZM241385 treatment. In addition, treatment with EHNA, which suppresses the breakdown of adenosine to inosine, enhanced the pain-relieving effects of the high-intensity swimming exercise. This is the first report demonstrating that repeated sessions of high-intensity swimming exercise attenuate mechanical allodynia in an animal model of CRPS-I and that the mechanism involves endogenous adenosine and adenosine A receptors. This study supports the use of high-intensity exercise as an adjunct therapy for CRPS-I treatment.
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PMID:High-intensity swimming exercise reduces neuropathic pain in an animal model of complex regional pain syndrome type I: evidence for a role of the adenosinergic system. 2329 54