Differential effects of adenosine receptor antagonists injected intrathecally on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the mouse.
A previous study reported that beta-endorphin and morphine administered supraspinally produce antinociception by activating different descending pain inhibitory systems. The present study was designed to investigate the blocking effects of A1 or A2 adenosine receptors in the spinal cord on antinociception induced by supraspinally administered mu- and epsilon-opioid receptor agonists. The effects of 1,3-dipropyl-8-(2-amino-4-chloro-phenyl)-xanthine (PACPX; an A1 adenosine receptor antagonist) or 3,7-dimethyl-1-propargylxanthine (DMPX; an A2 adenosine receptor antagonist) on the antinociception induced by morphine (a mu-opioid receptor agonist) or beta-endorphin (an epsilon-opioid receptor agonist) administered intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed by the tail-flick test. DMPX at doses of 1-40 micrograms (which administered intrathecally alone did not affect the latencies of tail-flick thresholds), attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered morphine (0.5 microgram) or beta-endorphin (1 microgram). PACPX at doses of 1-40 micrograms (which administered intrathecally alone did not affect the latencies of tail-flick thresholds), attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin but not morphine. These results suggest that A2 but not A1 adenosine receptors in the spinal cord may be involved in the antinociception induced by supraspinally administered morphine, while the antinociception induced by supraspinally administered beta-endorphin appears to be mediated by spinal A1 and A2 adenosine receptors. These results support the hypothesis that morphine and beta-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.
Suh
H W
HW
Department of Pharmacology, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea. hwsuh@sun.hallym.ac.kr
Song
D K
DK
Kim
Y H
YH
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011930:Reaction Time / Q000187:drug effects; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014970:Xanthines / Q000008:administration & dosage; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C057837:3,7-dimethyl-1-propargylxanthine; D001615:beta-Endorphin; D009020:Morphine; C106045:adenosine amine congener; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine; D013805:Theobromine