Assessment of the role of A1/A2 adenosine receptors mediating the purine antinociception, motor and autonomic function in the rat spinal cord

M. Sosnowski, C. W. Stevens, T. L. Yaksh

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Abstract

The effects on nociception, motor and autonomic function produced by the intrathecal administration of three adenosine analogs: N6-(L-2-phenylisopropyl)-adenosine, N6-cyclohexyladenosine and 5'-(N-ethylcarboxamido)-adenosine were examined in rats. Over the range of 0.3 to 1.0 nmol these agents produced a dose-dependent antinociception in the hot plate and tail-flick tests. In addition, 5'-(N-ethylcarboxamido)-adenosine and N6-(L-2-phenylisopropyl)-adenosine both suppressed the chemically evoked writhing response as well as the touch-evoked hyperesthesia normally observed in rats receiving low doses of intrathecal strychnine. These adenosine analogs examined at doses higher than 1.5 nmol produced a dose-dependent motor impairment as measured behaviorally and by electromyography, and an increase in the volume distention required to evoke micturition. Statistically significant effects on heart rate or blood pressure were not observed at any of the doses tested. The effects of the adenosine analogs on nociceptive and motor endpoints were partially antagonized by pretreatment with intrathecal caffeine (2 μmol). These results suggest a probable association of spinal adenosine receptors with a number of spinal sensory and motor systems other than those involved with nociceptive processing.

Original languageEnglish
Pages (from-to)915-922
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume250
Issue number3
StatePublished - 1 Jan 1989

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Adenosine A2 Receptors
Adenosine A1 Receptors
Adenosine
Spinal Cord
Hyperesthesia
Strychnine
Purinergic P1 Receptors
Nociception
Urination
Touch
Electromyography
purine
Caffeine
Tail
Heart Rate
Blood Pressure

Cite this

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abstract = "The effects on nociception, motor and autonomic function produced by the intrathecal administration of three adenosine analogs: N6-(L-2-phenylisopropyl)-adenosine, N6-cyclohexyladenosine and 5'-(N-ethylcarboxamido)-adenosine were examined in rats. Over the range of 0.3 to 1.0 nmol these agents produced a dose-dependent antinociception in the hot plate and tail-flick tests. In addition, 5'-(N-ethylcarboxamido)-adenosine and N6-(L-2-phenylisopropyl)-adenosine both suppressed the chemically evoked writhing response as well as the touch-evoked hyperesthesia normally observed in rats receiving low doses of intrathecal strychnine. These adenosine analogs examined at doses higher than 1.5 nmol produced a dose-dependent motor impairment as measured behaviorally and by electromyography, and an increase in the volume distention required to evoke micturition. Statistically significant effects on heart rate or blood pressure were not observed at any of the doses tested. The effects of the adenosine analogs on nociceptive and motor endpoints were partially antagonized by pretreatment with intrathecal caffeine (2 μmol). These results suggest a probable association of spinal adenosine receptors with a number of spinal sensory and motor systems other than those involved with nociceptive processing.",
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