Abstract
The intradermal injection of adenosine produces a dose-dependent decrease in mechanical nociceptive threshold in the hindpaw of the rat that is not attenuated by elimination of indirect pathways for the production of hyperalgesia. Adenosine-induced hyperalgesia is mimicked by the A 2-agonists, 5′-(N-ethyl)-carboxamido-adenosine and 2-phenylaminoadenosine but not by the A 1-agonist, N 6-cyclo-pentyladenosine and antagonized by the adenosine A 2-receptor antagonist, PD 081360-0002 but not by the A 1-antagonist, 1,3-dipropyl-8-(2-amino-4-chlorphenyl)xanthine. The latency to onset of adenosine and 2-phenylaminoadenosine hyperalgesia is similar to that produced by prostaglandin E 2, a directly acting hyperalgesic agent but shorter than that produced by leukotriene B 4, which acts indirectly. 2-Phenylaminoadenosine hyperalgesia is prolonged by rolipram, a phosphodiesterase inhibitor. Both 2-phenylaminoadenosine and prostaglandin E 2 hyperalgesia are antagonized by the A 1-agonist N 6-cyclo-pentyladenosine and the mu-agonist, [ d-Ala 2, NMe-Phe 4, Gly-ol]enkephalin. However, 1-acetyl-2-(8-chloro-10,11-dihydrodibenz[b,f]oxazepine-10-carbonyl)hydrazine, a prostaglandin-receptor antagonist, inhibits prostaglandin E 2 (Taiwo and Levine, Brain Res. 458, 402–406, 1988) but not 2-phenylamino-adenosine hyperalgesia and PD 081360-0002, the adenosine receptor antagonist, inhibits 2-phenylamino-adenosine but not prostaglandin E 2 hyperalgesia. These data suggest that adenosine is a directly acting agent that produces hyperalgesia by an action at the A 2-receptor and that this hyperalgesia is mediated by the cAMP second messenger.
Published Version
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