Linked Life Data

12151032

Source:http://linkedlifedata.com/resource/pubmed/id/12151032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-8-1
pubmed:abstractText
Inhibitors of adenosine kinase (AK) enhance extracellular concentrations of the inhibitory neuromodulator adenosine (ADO) at sites of tissue hyperexcitability and produce antinociceptive effects in animal models of pain and inflammation. The present study compared the ability of several novel and selective AK inhibitors and ADO receptor-selective agonists to attenuate carrageenan-induced thermal hyperalgesia and to impair motor performance as measured by effects on exploratory motor activity and rotorod performance. The prototypical nucleoside AK inhibitor, 5'deoxy-5-iodotubercidin (5'd-5IT), dose-dependently blocked thermal hyperalgesia (ED(50)=0.2 micromol/kg ip) and was 4- and 75-fold less potent in reducing exploratory motor activity and rotorod performance, respectively. The antihyperalgesic effects of 5'd-5IT were fully blocked by the A(1) antagonist, cyclopentyltheophylline (CPT) and the A(2A) antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). Novel nucleoside and non-nucleoside AK inhibitors (A-134974, A-286501 and ABT-702) also potently (ED(50)=0.7-2 micromol/kg ip) blocked carrageenan-induced thermal hyperalgesia and were significantly less potent than 5'd-5IT in impairing motor performance. The systemic administration of N(6)-cyclopentyladenosine (CPA), an A(1) receptor-selective agonist, CGS 21680, an A(2A) receptor-selective agonist, and N(6)-ethylcarboxamidoadenosine (NECA), a nonselective ADO receptor agonist potently reduced (ED(50)=0.3-1.0 micromol/kg ip) thermal hyperalgesia. Unlike the AK inhibitors, however, these ADO receptor agonists produced significant antinociception only at doses that also decreased motor performance. These data demonstrate that AK inhibitors produce specific antihyperalgesic effects via an interaction with ADO A(1) and A(2A) receptors at doses that lack detectable effects on exploratory motor activity and rotorod performance and offer an improved separation between antinociceptive and motor impairing effects as compared to ADO receptor agonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0091-3057
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
573-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Comparison of the ability of adenosine kinase inhibitors and adenosine receptor agonists to attenuate thermal hyperalgesia and reduce motor performance in rats.
pubmed:affiliation
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R04PM, AP9A/2, 100 Abbott Park Road, IL 60064-6123, USA. michael.jarvis@abbott.com
pubmed:publicationType
Journal Article, Comparative Study