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Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice.
J Pharmacol Exp Ther. 1992 Dec; 263(3):1097-104.JP

Abstract

Possible involvement of adenosine, as a secondary neurotransmitter, in opioid modulation of nociception and gastrointestinal function was investigated in mice. Inhibitory actions of theophylline, a nonselective adenosine receptor antagonist, were evaluated against effects evoked by opioid receptor-selective agonists administered at spinal or supraspinal sites. Intrathecal administration of theophylline significantly inhibited antinociceptive actions produced by intrathecal (i.th.) injections of morphine, [D-Ala2, NMPhe4, Gly-ol] enkephalin (DAMGO), [D-Pen2, D-Pen5] enkephalin (DPDPE) and beta-endorphin as measured with the warm water tail-flick assay. The rank order of rightward displacement of i.th. agonist dose-response curves by theophylline (i.th.) was DPDPE (greatest) > DAMGO > morphine > beta-endorphin. Theophylline was less effective as an inhibitor in the hot-plate assay. Additionally, i.th. administration of theophylline inhibited antinociceptive effects evoked by i.c.v. administration of opioids. The rank order of rightward displacement of dose-response curves after i.c.v. opioid administration was DAMGO (greatest) > beta-endorphin > morphine > DPDPE. In contrast to the effectiveness of theophylline administered i.th., theophylline coadministered i.c.v. with opioid agonists did not inhibit opioid-induced antinociception. Neither i.th. nor i.c.v. theophylline altered inhibitory effects on gastric emptying and gastrointestinal propulsion produced by i.th. or i.c.v. administration of selective opioid agonists. These data provide additional support for involvement of spinal adenosine as a secondary neurotransmitter in opioid antinociceptive processes associated with local spinal reflexes as well as in descending antinociceptive processes. Adenosine was not involved in modulation of opioid-activated gastrointestinal outflow pathways at either spinal or supraspinal levels.

Authors+Show Affiliations

DeLander GE
Department of Pharmacology, College of Pharmacy, Oregon State University, Corvallis.
Mosberg HI
No affiliation info available
Porreca F
No affiliation info available

MeSH

AdenosineAnalgesiaAnimalsEndorphinsEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Enkephalin, D-Penicillamine (2,5)-EnkephalinsGastric EmptyingGastrointestinal MotilityInjections, IntraventricularInjections, SpinalMaleMiceMice, Inbred ICRMorphineReceptors, OpioidSpinal CordTheophylline

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1335055

Citation

DeLander, G E., et al. "Involvement of Adenosine in Antinociception Produced By Spinal or Supraspinal Receptor-selective Opioid Agonists: Dissociation From Gastrointestinal Effects in Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 263, no. 3, 1992, pp. 1097-104.
DeLander GE, Mosberg HI, Porreca F. Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. J Pharmacol Exp Ther. 1992;263(3):1097-104.
DeLander, G. E., Mosberg, H. I., & Porreca, F. (1992). Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. The Journal of Pharmacology and Experimental Therapeutics, 263(3), 1097-104.
DeLander GE, Mosberg HI, Porreca F. Involvement of Adenosine in Antinociception Produced By Spinal or Supraspinal Receptor-selective Opioid Agonists: Dissociation From Gastrointestinal Effects in Mice. J Pharmacol Exp Ther. 1992;263(3):1097-104. PubMed PMID: 1335055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. AU - DeLander,G E, AU - Mosberg,H I, AU - Porreca,F, PY - 1992/12/1/pubmed PY - 1992/12/1/medline PY - 1992/12/1/entrez SP - 1097 EP - 104 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 263 IS - 3 N2 - Possible involvement of adenosine, as a secondary neurotransmitter, in opioid modulation of nociception and gastrointestinal function was investigated in mice. Inhibitory actions of theophylline, a nonselective adenosine receptor antagonist, were evaluated against effects evoked by opioid receptor-selective agonists administered at spinal or supraspinal sites. Intrathecal administration of theophylline significantly inhibited antinociceptive actions produced by intrathecal (i.th.) injections of morphine, [D-Ala2, NMPhe4, Gly-ol] enkephalin (DAMGO), [D-Pen2, D-Pen5] enkephalin (DPDPE) and beta-endorphin as measured with the warm water tail-flick assay. The rank order of rightward displacement of i.th. agonist dose-response curves by theophylline (i.th.) was DPDPE (greatest) > DAMGO > morphine > beta-endorphin. Theophylline was less effective as an inhibitor in the hot-plate assay. Additionally, i.th. administration of theophylline inhibited antinociceptive effects evoked by i.c.v. administration of opioids. The rank order of rightward displacement of dose-response curves after i.c.v. opioid administration was DAMGO (greatest) > beta-endorphin > morphine > DPDPE. In contrast to the effectiveness of theophylline administered i.th., theophylline coadministered i.c.v. with opioid agonists did not inhibit opioid-induced antinociception. Neither i.th. nor i.c.v. theophylline altered inhibitory effects on gastric emptying and gastrointestinal propulsion produced by i.th. or i.c.v. administration of selective opioid agonists. These data provide additional support for involvement of spinal adenosine as a secondary neurotransmitter in opioid antinociceptive processes associated with local spinal reflexes as well as in descending antinociceptive processes. Adenosine was not involved in modulation of opioid-activated gastrointestinal outflow pathways at either spinal or supraspinal levels. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1335055/Involvement_of_adenosine_in_antinociception_produced_by_spinal_or_supraspinal_receptor_selective_opioid_agonists:_dissociation_from_gastrointestinal_effects_in_mice_ DB - PRIME DP - Unbound Medicine ER -